File size: 46,015 Bytes
1ff81a7
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
143
144
145
146
147
148
149
150
151
152
153
154
155
156
157
158
159
160
161
162
163
164
165
166
167
168
169
170
171
172
173
174
175
176
177
178
179
180
181
182
183
184
185
186
187
188
189
190
191
192
193
194
195
196
197
198
199
200
201
202
203
204
205
206
207
208
209
210
211
212
213
214
215
216
217
218
219
220
221
222
223
224
225
226
227
228
229
230
231
232
233
234
235
236
237
238
239
240
241
242
243
244
245
246
247
248
249
250
251
252
253
254
255
256
257
258
259
260
261
262
263
264
265
266
267
268
269
270
271
272
273
274
275
276
277
278
279
280
281
282
283
284
285
286
287
288
289
290
291
292
293
294
295
296
297
298
299
300
301
302
303
304
305
306
307
308
309
310
311
312
313
314
315
316
317
318
319
320
321
322
323
324
325
326
327
328
329
330
331
332
333
334
335
336
337
338
339
340
341
342
343
344
345
346
347
348
349
350
351
352
353
354
355
356
357
358
359
360
361
362
363
364
365
366
367
368
369
370
371
372
373
374
375
376
377
378
379
380
381
382
383
384
385
386
387
388
389
390
391
392
393
394
395
396
397
398
399
400
401
402
403
404
405
406
407
408
409
410
411
412
413
414
415
416
417
418
419
420
421
422
423
424
425
426
427
428
429
430
431
432
433
434
435
436
437
438
439
440
441
442
443
444
445
446
447
448
449
450
451
452
453
454
455
456
457
458
459
460
461
462
463
464
465
466
467
468
469
470
471
472
473
474
475
476
477
478
479
480
481
482
483
484
485
486
487
488
489
490
491
492
493
494
495
496
497
498
499
500
501
502
503
504
505
506
507
508
509
510
511
512
513
514
515
516
517
518
519
520
521
522
523
524
525
526
527
528
529
530
531
532
533
534
535
536
537
538
539
540
541
542
543
544
545
546
547
548
549
550
551
552
553
554
555
556
557
558
559
560
561
562
563
564
565
566
567
568
569
570
571
572
573
574
575
576
577
578
579
580
581
582
583
584
585
586
587
588
589
590
591
592
593
594
595
596
597
598
599
600
601
602
603
604
605
606
607
608
609
610
611
612
613
614
615
616
617
618
619
620
621
622
623
624
625
626
627
628
629
630
631
632
633
634
635
636
637
638
639
640
641
642
643
644
645
646
647
648
649
650
651
652
653
654
655
656
657
658
659
660
661
662
663
664
665
666
667
668
669
670
671
672
673
674
675
676
677
678
679
680
681
682
683
684
685
686
687
688
689
690
691
692
693
694
695
696
697
698
699
700
701
702
703
704
705
706
707
708
709
710
711
712
713
714
715
716
717
718
719
720
721
722
723
724
725
726
727
728
729
730
731
732
733
734
735
736
737
738
739
740
741
742
743
744
745
746
747
748
749
750
751
752
753
754
755
756
757
758
759
760
761
762
763
764
765
766
767
768
769
770
771
772
773
774
775
776
777
778
779
780
781
782
783
784
785
786
787
788
789
790
791
792
793
794
795
796
797
798
799
800
801
802
803
804
805
806
807
808
809
810
811
812
813
814
815
816
817
818
819
820
821
822
823
824
825
826
827
828
829
830
831
832
833
834
835
836
837
838
839
840
841
842
843
844
845
846
847
848
849
850
851
852
853
854
855
856
857
858
859
860
861
862
863
864
865
866
867
868
869
870
871
872
873
874
875
876
877
878
879
880
881
882
883
884
885
886
887
888
889
890
891
892
893
894
895
896
897
898
899
900
901
902
903
904
905
906
907
908
909
910
911
912
913
914
915
916
917
918
919
920
921
922
923
924
925
926
927
928
929
930
931
932
933
934
935
936
937
938
939
940
941
942
943
944
945
946
947
948
949
950
951
952
953
954
955
956
957
958
959
960
961
962
963
964
965
966
967
968
969
970
971
972
973
974
975
976
977
978
979
980
981
982
983
984
985
986
987
988
989
990
991
992
993
994
995
996
997
998
999
1000
1001
1002
1003
1004
1005
1006
1007
1008
1009
1010
1011
1012
1013
1014
1015
1016
1017
1018
1019
1020
1021
1022
1023
1024
1025
1026
1027
1028
1029
1030
1031
1032
1033
1034
1035
1036
1037
1038
1039
1040
1041
1042
1043
1044
1045
1046
1047
1048
1049
1050
1051
1052
1053
1054
1055
1056
1057
1058
1059
1060
1061
1062
1063
1064
1065
1066
1067
1068
1069
1070
1071
1072
1073
1074
1075
1076
1077
1078
1079
1080
1081
1082
1083
1084
1085
1086
1087
1088
1089
1090
1091
1092
1093
1094
1095
1096
1097
1098
1099
1100
1101
1102
{
 "cells": [
  {
   "cell_type": "markdown",
   "id": "3288987d",
   "metadata": {},
   "source": [
    "# X-LoRA Inference: Gemma-7b model for molecular design \n"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "25beb240-1ae1-4537-9cc6-da621862d0bd",
   "metadata": {},
   "source": [
    "### Helper functions "
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "id": "e2c18b20-b1a9-4f3e-ae84-2a551e2ed69c",
   "metadata": {
    "tags": []
   },
   "outputs": [],
   "source": [
    "import os\n",
    "import random\n",
    "\n",
    "import torch\n",
    "from transformers import AutoModelForCausalLM, AutoTokenizer\n",
    "import transformers\n",
    "from datasets import load_dataset\n",
    "from datasets import IterableDataset\n",
    "\n",
    "from transformers import Trainer\n",
    "from transformers import TrainingArguments\n",
    "from transformers import DataCollatorWithPadding\n",
    "from transformers import TrainerCallback\n",
    "from transformers import AutoConfig\n",
    "from transformers import BitsAndBytesConfig\n",
    "\n",
    "from peft import LoraConfig, get_peft_model\n",
    "from torch.utils.data import Dataset\n",
    "from transformers import get_linear_schedule_with_warmup\n",
    "from accelerate import infer_auto_device_map\n",
    "import math\n",
    "import numpy as np\n",
    "import unidecode\n",
    "import pandas as pd\n",
    "from matplotlib import pyplot as plt\n",
    "import peft\n",
    "\n",
    "from tqdm.notebook import tqdm\n",
    "\n",
    "device='cuda'\n",
    "\n",
    "def params(model):\n",
    "    model_parameters = filter(lambda p: p.requires_grad, model.parameters())\n",
    "    params = sum([np.prod(p.size()) for p in model_parameters])\n",
    "\n",
    "    print(\"Number of model arameters: \", params) \n",
    "\n",
    "def generate_response (model,tokenizer,text_input=\"Biology offers amazing\",\n",
    "                      num_return_sequences=1,\n",
    "                      temperature=1., #the higher the temperature, the more creative the model becomes\n",
    "                      max_new_tokens=127,\n",
    "                      num_beams=1,\n",
    "                      top_k = 50,\n",
    "                      top_p =0.9,repetition_penalty=1.,eos_token_id=107,verbatim=False,\n",
    "                      exponential_decay_length_penalty_fac=None,add_special_tokens  =True, eos_token=None, \n",
    "                      ):\n",
    "\n",
    "    if eos_token==None:\n",
    "        eos_token=tokenizer('<end_of_turn>', add_special_tokens  =False,   ) ['input_ids'][0]\n",
    "        \n",
    "    inputs = tokenizer(text_input,  \n",
    "                              add_special_tokens  =add_special_tokens,  \n",
    "                              return_tensors ='pt').to(device)\n",
    "    if verbatim:\n",
    "        print (\"Length of input, tokenized: \", inputs[\"input_ids\"].shape, inputs[\"input_ids\"],\"eos_token: \", eos_token)\n",
    "    with torch.no_grad():\n",
    "          outputs = model.generate(#input_ids=inputs.to(device), \n",
    "                                   input_ids = inputs[\"input_ids\"],\n",
    "                                    attention_mask = inputs[\"attention_mask\"] , # This is usually done automatically by the tokenizer\n",
    "                                    max_new_tokens=max_new_tokens,\n",
    "                                   temperature=temperature, #value used to modulate the next token probabilities.\n",
    "                                   num_beams=num_beams,\n",
    "                                   top_k = top_k,\n",
    "                                   top_p = top_p,\n",
    "                                   num_return_sequences = num_return_sequences,\n",
    "                                   eos_token_id=eos_token,\n",
    "                                   pad_token_id = eos_token,\n",
    "                                   do_sample =True, \n",
    "                                   repetition_penalty=repetition_penalty, \n",
    "                                  )\n",
    "\n",
    "    return tokenizer.batch_decode(outputs[:,inputs[\"input_ids\"].shape[1]:].detach().cpu().numpy(), skip_special_tokens=True)\n",
    "\n",
    "def generate_answer (model,tokenizer,system='You a helpful assistant. You are familiar with materials science. ',\n",
    "                     q='What is spider silk in the context of bioinspired materials?',\n",
    "                        repetition_penalty=1.1,\n",
    "                                           top_p=0.1, top_k=32,  \n",
    "                                  temperature=.6,max_new_tokens=512, verbatim=False, eos_token=None,add_special_tokens=True,\n",
    "                     prepend_response='', messages=[],\n",
    "                                ):\n",
    "\n",
    "    if eos_token==None:\n",
    "        eos_token= tokenizer.eos_token_id\n",
    "        \n",
    "    if system==None:\n",
    "        messages.append ({\"role\": \"user\", \"content\": q} )\n",
    "    else:\n",
    "        messages.append ({\"role\": \"user\", \"content\": system+q})\n",
    "         \n",
    "    txt = tokenizer.apply_chat_template(messages, tokenize=False, add_generation_prompt=True, )\n",
    "    txt=txt+prepend_response\n",
    "     \n",
    "    output_text=generate_response (model,tokenizer,text_input=txt,eos_token_id=eos_token,\n",
    "                                  num_return_sequences=1,  repetition_penalty=repetition_penalty,\n",
    "                                           top_p=top_p, top_k=top_k,  add_special_tokens  =add_special_tokens,\n",
    "                                \n",
    "                                 temperature=temperature,max_new_tokens=max_new_tokens, verbatim=verbatim, \n",
    "                                            \n",
    "                                           )\n",
    "    return (  output_text[0] )"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "75d89d27-8386-4859-a36e-ce4842415b59",
   "metadata": {},
   "source": [
    "### Load X-LoRA Gemma model "
   ]
  },
  {
   "cell_type": "raw",
   "id": "cd1b66f6-1fe1-4b2c-9309-fe01d34d7d54",
   "metadata": {},
   "source": [
    "https://github.com/EricLBuehler/xlora"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "id": "12848c38-cc0c-41c7-bf04-9856730458df",
   "metadata": {},
   "outputs": [],
   "source": [
    "import torch\n",
    "from xlora.xlora_utils import load_model  \n",
    "\n",
    "XLoRa_model_name = 'lamm-mit/x-lora-gemma-7b'\n",
    "\n",
    "model, tokenizer=load_model(model_name = XLoRa_model_name, \n",
    "                           device='cuda:0',\n",
    "                           use_flash_attention_2=True, \n",
    "                           dtype=torch.bfloat16,\n",
    "                            )\n",
    "eos_token_id= tokenizer('<end_of_turn>', add_special_tokens=False, ) ['input_ids'][0]\n"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "b197ffd5-7752-4081-9227-c46a485afeec",
   "metadata": {},
   "source": [
    "### Inference using Guidance "
   ]
  },
  {
   "cell_type": "raw",
   "id": "f7009898-17a9-468a-970a-59d7c80553ca",
   "metadata": {},
   "source": [
    "https://github.com/guidance-ai/guidance"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "id": "80b62bf2-a424-4858-a321-f55e3327b070",
   "metadata": {},
   "outputs": [],
   "source": [
    "from guidance import models\n",
    "from guidance import gen, select, system, user, assistant,  newline\n",
    "from IPython.display import display, Markdown\n",
    "\n",
    "gpt = models.TransformersChat(model=model, tokenizer=tokenizer)\n",
    "gpt_question_asker = gpt"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "id": "1cb5a867-a127-45c2-b75b-35883a78930b",
   "metadata": {
    "scrolled": true
   },
   "outputs": [],
   "source": [
    "with user():        \n",
    "    lm =gpt + f\"\"\"List the most important biomolecules used in biological materials to make polymers with multifunctional qualities.\"\"\" \n",
    "\n",
    "with assistant():        \n",
    "    lm+=\"[\"+gen('res1', max_tokens=1024)"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "a841c58c-bded-4741-80df-66ca434bfac0",
   "metadata": {},
   "source": [
    "### Inference using Hugging Face generate functions  "
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "id": "26a27dc2-4e28-4fee-b37c-446281cd23da",
   "metadata": {
    "scrolled": true
   },
   "outputs": [],
   "source": [
    "system_prompt='You are an expert in biological molecular engineering. '\n",
    "q=\"\"\"\n",
    "What are potential molecular engineering approaches to create better materials? Name specific molecules of interest.\n",
    "\"\"\"\n",
    "\n",
    "res=generate_answer (model, tokenizer,system=system_prompt,\n",
    "                     q=q,\n",
    "                     repetition_penalty=1.,  top_p=0.9, top_k=256,  \n",
    "                     temperature=.5,max_new_tokens=512, verbatim=False, \n",
    "                )\n",
    "\n",
    "display (Markdown (\"## X-LoRA:\\n\\n\"+res))"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "id": "82d162fe-6149-44d4-afbe-63213b10f183",
   "metadata": {},
   "outputs": [],
   "source": [
    "system_prompt='You are an expert in biological molecular engineering. '\n",
    "q=\"\"\"\n",
    "List the most important biomolecules used in biological materials to make polymers with multifunctional qualities.\n",
    "\"\"\"\n",
    "messages=[]\n",
    "res=generate_answer (model, tokenizer,system=system_prompt,\n",
    "                     q=q,   repetition_penalty=1., top_p=0.9, top_k=256,    temperature=.5,max_new_tokens=512, verbatim=False,messages=messages  )\n",
    "\n",
    "display (Markdown (\"## X-LoRA:\\n\\n\"+res))\n",
    "messages.append ({\"role\": \"assistant\", \"content\": res} )"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "id": "f9ad8c01-7cfd-4017-a8af-0b72b4ea25fe",
   "metadata": {},
   "outputs": [],
   "source": [
    "system_prompt=None\n",
    "q=\"\"\"\n",
    "How does chitin form a material, specifically in terms of molecular interactions? \n",
    "\"\"\" \n",
    "res=generate_answer (model, tokenizer,system=system_prompt,\n",
    "                     q=q,   repetition_penalty=1., top_p=0.9, top_k=256,    temperature=.1,max_new_tokens=512, verbatim=False,messages=messages,\n",
    "                )\n",
    "\n",
    "display (Markdown (\"## X-LoRA:\\n\\n\"+res))\n",
    "messages.append ({\"role\": \"assistant\", \"content\": res} )"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "id": "6f520fd9-0d06-4971-9b58-74d8d2c3e2ef",
   "metadata": {},
   "outputs": [],
   "source": [
    "system_prompt=None\n",
    "q=\"\"\"\n",
    "Thank you. What are potential chemical modifications of N-acetylglucosamine units that would improve mechanical properties?\n",
    "\"\"\" \n",
    "res=generate_answer (model, tokenizer,system=system_prompt,\n",
    "                     q=q,   repetition_penalty=1., top_p=0.9, top_k=256,    temperature=.1,max_new_tokens=512, verbatim=False,messages=messages,\n",
    "                )\n",
    "\n",
    "display (Markdown (\"## X-LoRA:\\n\\n\"+res))\n",
    "messages.append ({\"role\": \"assistant\", \"content\": res} )"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "ce5a2293-b66d-4ef6-987e-451dc1a92621",
   "metadata": {},
   "source": [
    "### Molecule design examples"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "id": "e547bed4-da94-48c7-b9dd-00da7732ef20",
   "metadata": {
    "scrolled": true
   },
   "outputs": [],
   "source": [
    "import pandas as pd\n",
    "from sklearn.preprocessing import MinMaxScaler\n",
    "\n",
    "df_smiles=pd.read_csv ('./QM9.csv')\n",
    "SMILES_LIST=list (df_smiles['smiles'])\n",
    "\n",
    "X = df_smiles.iloc[:, 0].values.reshape(-1, 1)  # Input feature, reshaped for compatibility\n",
    "y = df_smiles.iloc[:, 1:]  # Target features\n",
    "\n",
    "# Scaling the target features\n",
    "scaler = MinMaxScaler()\n",
    "y_scaled = scaler.fit_transform(y)\n",
    "\n",
    "from sklearn.model_selection import train_test_split\n",
    "\n",
    "X_train, X_test, y_train, y_test= train_test_split(X, y_scaled, test_size=0.2, random_state=42)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "id": "44c43109-0606-42d2-a1b6-01278ff6432f",
   "metadata": {
    "scrolled": true
   },
   "outputs": [],
   "source": [
    "import os\n",
    "import numpy as np\n",
    "import pandas as pd\n",
    "import matplotlib.pyplot as plt\n",
    "import seaborn as sns\n",
    "from sklearn.metrics import mean_squared_error\n",
    "labels = [\"mu\", \"alpha\", \"homo\", \"lumo\", \"gap\", \"r2\", \"zpve\", \"cv\", \"u0\", \"u298\", \"h298\", \"g298\"]\n",
    "\n",
    "def return_str(vals=np.array ([.1, .5, .6, 2.])):\n",
    "    ch=''\n",
    "    for i in range (len (vals)):\n",
    "        ch=ch+f'{vals[i]:1.3f},'\n",
    "        \n",
    "    return ch[:-1]   \n",
    "\n",
    "def extract_start_and_end(string_input, start_token='[', end_token=']'):\n",
    "    \"\"\"\n",
    "    Extracts the substring from 'string_input' that is enclosed between the first occurrence of\n",
    "    'start_token' and the last occurrence of 'end_token'.\n",
    "\n",
    "    Args:\n",
    "    string_input (str): The string from which to extract the substring.\n",
    "    start_token (str): The starting delimiter. Default is '['.\n",
    "    end_token (str): The ending delimiter. Default is ']'.\n",
    "\n",
    "    Returns:\n",
    "    str: The extracted substring. If 'start_token' or 'end_token' is not found, returns an empty string.\n",
    "    \"\"\"\n",
    "    # Find the index of the first occurrence of start_token\n",
    "    i = string_input.find(start_token)\n",
    "    # Find the index of the last occurrence of end_token\n",
    "    j = string_input.rfind(end_token)\n",
    "\n",
    "    # Check if both tokens are found and i < j to ensure proper enclosure\n",
    "    if i == -1 or j == -1 or i >= j:\n",
    "        return \"\"\n",
    "    else:\n",
    "        # Extract and return the content between the first start_token and the last end_token\n",
    "        return string_input[i + 1:j]\n",
    "\n",
    "def is_SMILES_novel (SMILES, SMILES_LIST=None):\n",
    "\n",
    "    if SMILES_LIST !=None:\n",
    "        \n",
    "        if SMILES not in SMILES_LIST:\n",
    "            is_novel=True\n",
    "        else:\n",
    "            is_novel=False\n",
    "    else:\n",
    "        is_novel=None\n",
    "    return is_novel\n",
    "    \n",
    "def visualize_SMILES (smiles_code, dir_path='./' , root='', sample_count=0):\n",
    "    molecule = Chem.MolFromSmiles(smiles_code)\n",
    "                    \n",
    "    # Generate an image of the molecule\n",
    "    molecule_image = Draw.MolToImage(molecule)\n",
    "    \n",
    "    # Display the image directly in Jupyter Notebook\n",
    "    display(molecule_image)\n",
    "    \n",
    "    image_path=f\"{dir_path}/SMILES_{sample_count}_{root}_molecule_image.png\"\n",
    "    molecule_image.save(image_path)\n",
    "\n",
    "    return image_path\n",
    "\n",
    "\n",
    "def design_from_target(\n",
    "    model,\n",
    "    tokenizer,\n",
    "    target,\n",
    "    temperature=0.1,\n",
    "    num_beams=1,\n",
    "    top_k=50,\n",
    "    top_p=0.95,\n",
    "    repetition_penalty=1.0,\n",
    "    messages=[]\n",
    "):\n",
    "    # Format the target line for molecular property generation\n",
    "    line = f'GenerateMolecularProperties<{return_str(target)}>'\n",
    "    \n",
    "    # Add the line to the message history\n",
    "    messages.append({\"role\": \"user\", \"content\": line})\n",
    "    \n",
    "    # Apply chat template with optional tokenization\n",
    "    line = tokenizer.apply_chat_template(messages, tokenize=False, add_generation_prompt=True)\n",
    "    \n",
    "    # Generate response with specified parameters\n",
    "    result = generate_response(\n",
    "        model,\n",
    "        tokenizer,\n",
    "        text_input=line,\n",
    "        num_return_sequences=1,\n",
    "        temperature=temperature,\n",
    "        top_k=top_k,\n",
    "        top_p=top_p,\n",
    "        max_new_tokens=256\n",
    "    )[0]\n",
    "    \n",
    "    return result\n",
    "\n",
    "def properties_from_SMILES(\n",
    "    model,\n",
    "    tokenizer,\n",
    "    target,\n",
    "    temperature=0.1,\n",
    "    top_k=128,\n",
    "    top_p=0.9,\n",
    "    num_beams=1,\n",
    "    repetition_penalty=1.0\n",
    "):\n",
    "    # Format the target line for molecular property calculation\n",
    "    line = f'CalculateMolecularProperties<{target}>'\n",
    "    \n",
    "    # Initialize messages and add the formatted line\n",
    "    messages = [{\"role\": \"user\", \"content\": line}]\n",
    "    \n",
    "    # Apply chat template with optional tokenization\n",
    "    line = tokenizer.apply_chat_template(messages, tokenize=False, add_generation_prompt=True)\n",
    "    \n",
    "    # Generate response with specified parameters\n",
    "    result = generate_response(\n",
    "        model,\n",
    "        tokenizer,\n",
    "        text_input=line,\n",
    "        num_return_sequences=1,\n",
    "        temperature=temperature,\n",
    "        top_k=top_k,\n",
    "        top_p=top_p,\n",
    "        max_new_tokens=256\n",
    "    )[0]\n",
    "    \n",
    "    # Extract relevant part of the result and convert to float list\n",
    "    result = extract_start_and_end(result, start_token='[', end_token=']')\n",
    "    return [float(i) for i in result.split(',')]\n",
    "\n",
    "  \n",
    "def avg_properties_from_SMILES (model, tokenizer, SMILES ='O=C(N)C1OC(CO)C(O)C(O)C1O', SMILES_dir='./',\n",
    "                                temperature=0.01, top_k=50,top_p=0.95, num_beams=1,   repetition_penalty=1.,\n",
    "                                labels=None, N_prop=6, plot_results=True):\n",
    "    if not os.path.exists(SMILES_dir):\n",
    "        os.makedirs(SMILES_dir)    \n",
    "    properties=[]\n",
    "    if labels==None and plot_results:\n",
    "        labels= ['mu',\n",
    "                 'alpha',\n",
    "                 'homo',\n",
    "                 'lumo',\n",
    "                 'gap',\n",
    "                 'r2',\n",
    "                 'zpve',\n",
    "                 'cv',\n",
    "                 'u0',\n",
    "                 'u298',\n",
    "                 'h298',\n",
    "                 'g298']\n",
    "    successful=0\n",
    "    for i in tqdm(range (N_prop)):\n",
    "        \n",
    "        try:\n",
    "            _prop=properties_from_SMILES (model, tokenizer, SMILES,temperature=temperature, top_k=top_k,top_p=top_p,\n",
    "                                          num_beams=num_beams, repetition_penalty=repetition_penalty,\n",
    "                                         )\n",
    "            if len (_prop)==len (labels):\n",
    "        \n",
    "                properties.append(np.array( _prop) )\n",
    "                successful+=1\n",
    "        except:\n",
    "            print (end=\"\")\n",
    "             \n",
    "    all_properties = np.array(properties)\n",
    "    \n",
    "    # Calculate mean and standard deviation for each property\n",
    "    means = np.mean(all_properties, axis=0)\n",
    "    std_devs = np.std(all_properties, axis=0)\n",
    "    \n",
    "    # Labels for the x-axis\n",
    "    if plot_results: \n",
    "        # Creating the plot with error bars\n",
    "        plt.figure(figsize=(6, 4))\n",
    "        plt.errorbar(labels, means, yerr=std_devs, fmt='o', ecolor='red', capsize=5, capthick=2, marker='s', color='blue')\n",
    "        plt.xticks(rotation=45)\n",
    "        plt.xlabel('Property')\n",
    "        plt.ylabel('Value')\n",
    "        plt.title('Average Properties with Error Bars')\n",
    "        plt.tight_layout()\n",
    "        plt.savefig(SMILES_dir + f\"avg_prop_{SMILES}.svg\", format=\"svg\")\n",
    "        \n",
    "        plt.show()\n",
    "        print (f\"Successful attempts: {successful}/{N_prop}\")\n",
    "        \n",
    "    return means, std_devs        \n",
    "\n",
    "def is_valid_smiles(smiles):\n",
    "    # This function tries to create a molecule object from a SMILES string.\n",
    "    # If the molecule object is created successfully and is not None, the SMILES is valid.\n",
    "    mol = Chem.MolFromSmiles(smiles)\n",
    "    return mol is not None\n",
    "    \n",
    "def design_molecule(model, tokenizer, target=None, temperature=0.1,\n",
    "             num_beams=1,top_k=50,top_p=0.95,  repetition_penalty=1.,\n",
    "                   SMILES_LIST=None, dir_path='./', messages=[],N_attempts_for_forward=1):\n",
    "\n",
    "    if not os.path.exists(dir_path):\n",
    "        os.makedirs(dir_path)\n",
    "    if target.any()==None:\n",
    "        target = np.random.rand(12)\n",
    "    \n",
    "    try:\n",
    "        SMILES=design_from_target (model, tokenizer, target, messages=messages)\n",
    "    except:\n",
    "        SMILES=None\n",
    "        print (\"Generation failed.\")\n",
    "\n",
    "    is_novel=is_SMILES_novel (SMILES, SMILES_LIST)\n",
    "    print (\"Result: \", SMILES, \"is novel: \", is_novel, \"is valid: \", is_valid_smiles(SMILES))\n",
    "    try:\n",
    "        visualize_SMILES (SMILES, dir_path=dir_path)\n",
    "    except:\n",
    "        print (\"Vis failed.\")\n",
    "\n",
    "    try:\n",
    "        if N_attempts_for_forward==1:\n",
    "            predicted = properties_from_SMILES(model, tokenizer, SMILES,temperature_pred, num_beams,\n",
    "                                            top_k, top_p, repetition_penalty)\n",
    "        else:\n",
    "            predicted,_=avg_properties_from_SMILES(model, tokenizer, SMILES, SMILES_dir=SMILES_dir,\n",
    "                                temperature=temperature_pred, top_k=top_k,top_p=top_p, num_beams=num_beams,   repetition_penalty=repetition_penalty,\n",
    "                                labels=labels, N_prop=N_attempts_for_forward, plot_results=False)\n",
    "\n",
    "        sns.set_style(\"whitegrid\")\n",
    "        plt.gcf().set_facecolor('white')\n",
    "        # Assuming GT_res and predictions are your data arrays/lists for Ground Truth and Predictions respectively\n",
    "        \n",
    "        x = np.arange(len(labels))  # Label locations\n",
    "        width = 0.35  # Width of the bars\n",
    "        \n",
    "        fig, ax = plt.subplots(figsize=(9, 5))\n",
    "        rects1 = ax.bar(x - width/2, target, width, label='Target')\n",
    "        rects2 = ax.bar(x + width/2, predicted, width, label='Predicted properties')\n",
    "        \n",
    "        # Add some text for labels, title and custom x-axis tick labels, etc.\n",
    "        ax.set_ylabel('Values')\n",
    "        ax.set_title('Comparison of Target and Predicted Properties')\n",
    "        ax.set_xticks(x)\n",
    "        ax.set_xticklabels(labels, rotation=45, ha=\"right\")\n",
    "        ax.legend()\n",
    "\n",
    "    except:\n",
    "        print(\"Forward anaysis failed.\")\n",
    "    return SMILES, is_novel\n",
    "\n",
    "def design_molecule_loop(model, tokenizer, target=None, temperature_gen=0.3,temperature_pred=0.01, SMILES_LIST=None,\n",
    "                           top_k=50, top_p=0.95, repetition_penalty=1., num_beams=1,update_primer_with_better_draft=False,\n",
    "                         threshold=0.01, N_max=100, dir_path='./',lower_bound = 0.0,remove_duplicates=True,\n",
    "                upper_bound = 0.1,sample_count=0, messages=[], N_attempts_for_forward=1, set_opt=None):\n",
    "\n",
    "    mse_smallest_current=9999\n",
    "    if not os.path.exists(dir_path):\n",
    "        os.makedirs(dir_path)\n",
    "    if target is None or not target.any():\n",
    "        target = np.random.rand(12)\n",
    "\n",
    "    if len (messages) >0:\n",
    "        print (\"Using primed generation:\\n\", messages)\n",
    "    \n",
    "    records = []  # To store SMILES, properties, and MSE\n",
    "    for iteration in range(N_max):\n",
    "        try:\n",
    "            print (f\">>> Iteration={iteration}\")\n",
    "            original_messages=copy.deepcopy (messages)\n",
    "\n",
    "            SMILES = design_from_target(model, tokenizer, target, temperature_gen, num_beams,\n",
    "                                        top_k, top_p, repetition_penalty, messages=original_messages)\n",
    "            is_novel=is_SMILES_novel (SMILES, SMILES_LIST)\n",
    "\n",
    "            if is_novel and is_valid_smiles(SMILES):\n",
    "                print (f\"{SMILES} is novel: {is_novel}\", \"is valid: \", {is_valid_smiles(SMILES)})\n",
    "                if N_attempts_for_forward==1:\n",
    "                    predicted = properties_from_SMILES(model, tokenizer, SMILES,temperature_pred, num_beams,\n",
    "                                                top_k, top_p, repetition_penalty)\n",
    "                else:\n",
    "                    predicted,_=avg_properties_from_SMILES(model, tokenizer, SMILES, SMILES_dir=dir_path,\n",
    "                                    temperature=temperature_pred, top_k=top_k,top_p=top_p,    repetition_penalty=repetition_penalty,\n",
    "                                    labels=labels, N_prop=N_attempts_for_forward, plot_results=False)\n",
    "\n",
    "                if set_opt==None:\n",
    "                    mse = mean_squared_error(target, predicted)\n",
    "                else:\n",
    "                    mse = mean_squared_error(target[set_opt], predicted[set_opt])\n",
    "                if mse<mse_smallest_current:\n",
    "                    mse_smallest_current=mse\n",
    "                    if update_primer_with_better_draft:\n",
    "                        messages=prime_messages (SMILES, predicted , N=1)\n",
    "                        print (\"Smaller MSE found, updated messages primer! Messages: \", messages,\n",
    "                          f\"\\n\\nCurrent MSE: {mse}\")\n",
    "                \n",
    "                records.append((SMILES, predicted, mse, is_novel))\n",
    "            \n",
    "                print (f\">>>Iteration={iteration}, MSE={mse} for SMILES={SMILES}, novel={is_novel}\")\n",
    "                if mse < threshold:\n",
    "                    print(f\"Threshold met at iteration {iteration+1}\")\n",
    "                    break\n",
    "            else:\n",
    "                print (f\"{SMILES} is not novel or not valid, validity: {is_valid_smiles(SMILES)}.\")\n",
    "        except Exception as e:\n",
    "            print(f\"Error during iteration {iteration+1}: {e}\")\n",
    "            continue\n",
    "\n",
    "    # Sorting records based on MSE (most accurate first)\n",
    "    records.sort(key=lambda x: x[2])\n",
    "\n",
    "    # Visualizing the best performing molecule\n",
    "    best_SMILES, best_predicted, best_mse, is_novel = records[0]\n",
    "\n",
    "    print (\"Best SILES: \", best_SMILES)\n",
    "    try:\n",
    "        print (f\"{best_SMILES} is novel: {is_novel}\")\n",
    "        \n",
    "        sns.set_style(\"whitegrid\")\n",
    "    \n",
    "        visualize_pred_vs_target (target, best_predicted, labels, dir_path=dir_path, best_SMILES=best_SMILES,sample_count=0)\n",
    "         \n",
    "        print(f\"Process completed. Results saved to {csv_path}.\") \n",
    "        visualize_SMILES(best_SMILES, dir_path=dir_path, root=f'{target}_BEST')\n",
    "\n",
    "        print(f\"Compute molecular structure, UFF eq, Gasteiger, etc.\") \n",
    "        \n",
    "        compute_gasteiger (best_SMILES, SMILES_dir=dir_path, target= np.array(best_predicted))\n",
    "\n",
    "        mol = Chem.MolFromSmiles(best_SMILES)\n",
    "        inchi_str = Chem.MolToInchi(mol)\n",
    "        print(f\"InChI String of {best_SMILES}:\", inchi_str)\n",
    "    \n",
    "           \n",
    "    except Exception as e:\n",
    "        print(f\"Processing/visualization failed for {best_SMILES}: {e}\")\n",
    "\n",
    "    # Writing records to a CSV file\n",
    "    df = pd.DataFrame(records, columns=['SMILES', 'Predicted Properties', 'MSE', 'is_novel'])\n",
    "    csv_path = os.path.join(dir_path, 'SMILES_designs.csv')\n",
    "    df.to_csv(csv_path, index=False)\n",
    "\n",
    "    # Plot MSE against the index (which now corresponds to the ranking)\n",
    "    plt.figure(figsize=(10, 8))  # Adjust the size as needed\n",
    "    plt.plot(df['SMILES'], df['MSE'], 'o', markersize=5)  # 'o' for circular markers\n",
    "    \n",
    "    # Adding labels for each point with the SMILES string\n",
    "    for i, txt in enumerate(df['SMILES']):\n",
    "        plt.annotate(txt, (i, df['MSE'].iloc[i]), fontsize=8, rotation=45, ha='right')\n",
    "    \n",
    "    visualize_over_SMILES (df,N_max=N_max,SMILES_dir=SMILES_dir,\n",
    "            lower_bound = lower_bound,remove_duplicates=remove_duplicates,\n",
    "                upper_bound = upper_bound, target=target)\n",
    "    return df \n",
    "\n",
    "from rdkit import Chem\n",
    "from rdkit.Chem import Draw\n",
    "import os\n",
    "\n",
    "def visualize_smiles_and_save(smiles_list, per_row=4, dir_path='./', root=''):\n",
    "    \"\"\"\n",
    "    Visualizes a list of molecules from their SMILES strings with labels, checks for validity, \n",
    "    and saves the visualization as an SVG file.\n",
    "    \n",
    "    Parameters:\n",
    "    - smiles_list: List of SMILES strings to visualize.\n",
    "    - per_row: Number of molecule images per row in the assembly.\n",
    "    - dir_path: Directory path where the SVG file will be saved.\n",
    "    \"\"\"\n",
    "    if not os.path.exists(dir_path):\n",
    "        os.makedirs(dir_path)\n",
    "    valid_molecules = []\n",
    "    valid_smiles = []  # To store valid SMILES strings for labeling\n",
    "    for smile in smiles_list:\n",
    "        mol = Chem.MolFromSmiles(smile)\n",
    "        if mol:  # If the molecule is valid\n",
    "            valid_molecules.append(mol)\n",
    "            valid_smiles.append(smile)  # Add the valid SMILES string\n",
    "    \n",
    "    # Proceed only if there are valid molecules\n",
    "    if not valid_molecules:\n",
    "        print(\"No valid molecules found in the provided SMILES strings.\")\n",
    "        return\n",
    "    \n",
    "    # Ensure the directory exists\n",
    "    if not os.path.exists(dir_path):\n",
    "        os.makedirs(dir_path)\n",
    "    \n",
    "    # Define the SVG file path\n",
    "    svg_file_path = os.path.join(dir_path, f'molecules_with_labels_{root}.svg')\n",
    "    \n",
    "    # Use RDKit to draw the molecules grid with labels\n",
    "    fig = Draw.MolsToGridImage(valid_molecules, molsPerRow=per_row, subImgSize=(200, 200), \n",
    "                               legends=valid_smiles, useSVG=True)\n",
    "    \n",
    "    # Saving the SVG content to a file\n",
    "    with open(svg_file_path, 'w') as svg_file:\n",
    "        svg_file.write(fig.data)\n",
    "    display (fig)\n",
    "    \n",
    "    print(f\"Visualization saved as SVG at: {svg_file_path}\")\n",
    "\n",
    "    return valid_smiles \n",
    "\n",
    "def plot_MSE_over_SMILES (df_design,N_max=24,\n",
    "            lower_bound = 0.0,\n",
    "                upper_bound = 0.08, SMILES_dir='./', target='',  ):\n",
    "    \n",
    "    if not os.path.exists(SMILES_dir):\n",
    "        os.makedirs(SMILES_dir)    \n",
    "    df_sorted = df_design[:N_max].sort_values('MSE',ascending=False).reset_index(drop=True)\n",
    "\n",
    "    \n",
    "    df_plot=df_sorted[(df_sorted['MSE'] > lower_bound) & (df_sorted['MSE'] < upper_bound)]\n",
    "    \n",
    "    # Plot MSE against the index (which now corresponds to the ranking)\n",
    "    fig, ax = plt.subplots(figsize=(8, 7))\n",
    "    plt.plot(df_plot['SMILES'], df_plot['MSE'], 'o-', markersize=5, )  # 'o' for circular markers\n",
    "    \n",
    "    # Improving the plot aesthetics\n",
    "    plt.xticks(rotation=90)  # Rotate the x-axis labels for better readability\n",
    "    plt.xlabel('Molecule SMILES')\n",
    "    plt.ylabel('MSE')\n",
    "    #plt.title('Ordered from Best to Worst')\n",
    "    plt.tight_layout()  # Adjust the layout to make room for the rotated x-axis labels\n",
    "    plt.savefig(SMILES_dir+f'SMILES_over_MSE_{target}.svg', format='svg')\n",
    "    plt.show()\n",
    "    \n",
    "def visualize_over_SMILES (df_design,N_max=24,per_row=20,SMILES_dir='./',\n",
    "            lower_bound = 0.0,\n",
    "                upper_bound = 0.08, target='', remove_duplicates=True):\n",
    "\n",
    "    if remove_duplicates:\n",
    "        # Example: Keep the entry with the best MSE among the novel molecules for each SMILES\n",
    "        df_design = df_design.sort_values(['MSE', 'is_novel', 'SMILES', ], ascending=[True, False, True]) \\\n",
    "             .drop_duplicates(subset='SMILES', keep='first')\n",
    "\n",
    "        df_design.reset_index(drop=True, inplace=True)\n",
    "        df_design.to_csv(f'{SMILES_dir}/sorted_noduplicates_{N_max}.csv', index=False)\n",
    "         \n",
    "    valid_smiles=visualize_smiles_and_save(list(df_design['SMILES'][:N_max]), per_row=per_row, dir_path=SMILES_dir, root=f'{target}')\n",
    "    \n",
    "    smiles_df = pd.DataFrame(valid_smiles, columns=[\"SMILES\"])\n",
    "\n",
    "    # Save the DataFrame to a CSV file\n",
    "    file_path = \"/smiles_data.csv\"\n",
    "    smiles_df.to_csv(f'{SMILES_dir}/valid_SMILES_{N_max}.csv', index=False )\n",
    "    \n",
    "    fig, ax = plt.subplots(figsize=(8, 5))\n",
    "    \n",
    "    df_plot=df_design[(df_design['MSE'] > lower_bound) & (df_design['MSE'] < upper_bound)]\n",
    "    df_plot.plot(kind='kde', color='darkblue', label='KDE', ax=ax)\n",
    "    \n",
    "    # Plot histogram with density=True for probability density representation\n",
    "    plt.hist(df_design['MSE'], density=True, alpha=0.5, color='skyblue', label='Histogram',bins=50, \n",
    "             range=[lower_bound,upper_bound]\n",
    "            )\n",
    "    plt.xlim(lower_bound, upper_bound)\n",
    "    plt.title('Density and Histogram Plot of MSE')\n",
    "    plt.xlabel('MSE')\n",
    "    plt.ylabel('Density')\n",
    "    \n",
    "    # Adding a legend to distinguish between the KDE and Histogram\n",
    "    plt.legend()\n",
    "    \n",
    "    plt.savefig(SMILES_dir+f'mse_histogram_{target}.svg', format='svg')\n",
    "    plt.show()\n",
    "\n",
    "    plot_MSE_over_SMILES (df_design,N_max=N_max,\n",
    "            lower_bound = lower_bound,\n",
    "                upper_bound = upper_bound, target=target,SMILES_dir=SMILES_dir)\n",
    "    \n",
    "    return df_design\n",
    "\n",
    "import numpy as np\n",
    "import matplotlib.pyplot as plt\n",
    "import pandas as pd\n",
    "from pandas.plotting import parallel_coordinates\n",
    "\n",
    "def plot_change_in_design(original, labels, target, SMILES_dir='./'):\n",
    "    if not os.path.exists(SMILES_dir):\n",
    "        os.makedirs(SMILES_dir)\n",
    "    \n",
    "    # Create a DataFrame to hold the original and target vectors with labels\n",
    "    df = pd.DataFrame([original, target], columns=labels)\n",
    "    df['Version'] = ['Original', 'Target']  # Add a 'Version' column for coloring\n",
    "    \n",
    "    # Plotting\n",
    "    plt.figure(figsize=(7, 4))\n",
    "    parallel_coordinates(df, 'Version', color=['blue', 'red'])\n",
    "    plt.title('Original vs Target Values across Properties')\n",
    "    plt.xticks(rotation=45)\n",
    "    plt.tight_layout()\n",
    "    \n",
    "    # Annotating changes with thicker arrows pointing towards the target\n",
    "    for i, label in enumerate(labels):\n",
    "        if original[i] < target[i]:  # If the target value is greater, arrow points upwards\n",
    "            plt.annotate('', xy=(i, target[i]), xytext=(i, original[i]),\n",
    "                         arrowprops=dict(arrowstyle=\"->\", color='black', lw=2))\n",
    "        else:  # If the target value is lesser, arrow points downwards\n",
    "            plt.annotate('', xy=(i, target[i]), xytext=(i, original[i]),\n",
    "                         arrowprops=dict(arrowstyle=\"->\", color='black', lw=2))\n",
    "    \n",
    "    # Save the plot as an SVG file in the specified directory\n",
    "    plt.savefig(SMILES_dir + \"parallel_coordinates_changes_direction.svg\", format=\"svg\")\n",
    "    \n",
    "    plt.show()\n",
    "    \n",
    "def visualize_pred_vs_target (target, best_predicted, labels, dir_path='./', best_SMILES='',sample_count=0):                           \n",
    "    if not os.path.exists(dir_path):\n",
    "        os.makedirs(dir_path)\n",
    "    sns.set_style(\"whitegrid\")\n",
    "    plt.gcf().set_facecolor('white')\n",
    "    \n",
    "    x = np.arange(len(labels))  # Label locations\n",
    "    width = 0.35  # Width of the bars\n",
    "    \n",
    "    fig, ax = plt.subplots(figsize=(9, 5))\n",
    "    rects1 = ax.bar(x - width/2, target, width, label='Target')\n",
    "    rects2 = ax.bar(x + width/2, best_predicted, width, label='Predicted properties')\n",
    "    \n",
    "    # Add some text for labels, title and custom x-axis tick labels, etc.\n",
    "    ax.set_ylabel('Values')\n",
    "    ax.set_title(f'Comparison of Target and Predicted Properties, {best_SMILES}')\n",
    "    ax.set_xticks(x)\n",
    "    ax.set_xticklabels(labels, rotation=45, ha=\"right\")\n",
    "    ax.legend()\n",
    "    fig.tight_layout()\n",
    "    plt.savefig(f\"{dir_path}/QM9_best_design_{target}_barplot_{sample_count}.svg\")\n",
    "    plt.show()\n",
    "    #plt.show()\n",
    "\n",
    "from rdkit import Chem\n",
    "from rdkit.Chem import AllChem, Draw\n",
    "from rdkit.Chem import AllChem, rdDepictor\n",
    "from rdkit.Chem.Draw import rdMolDraw2D\n",
    " \n",
    "def prime_messages (SMILES_chitin_monomer, target, N=1):\n",
    "    messages=[]\n",
    "    for i in range (N):\n",
    "        \n",
    "        line=f'GenerateMolecularProperties<{return_str( target)}>'\n",
    "        messages.append ({\"role\": \"user\", \"content\": line},  )\n",
    "        line=f'[{SMILES_chitin_monomer}]'\n",
    "        messages.append ({\"role\": \"assistant\", \"content\": line},  )\n",
    "        \n",
    "    return messages\n",
    "\n",
    "from rdkit import Chem\n",
    "from rdkit.Chem import AllChem\n",
    "\n",
    "def smiles_to_3d(smiles, num_confs=100):\n",
    "    mol = Chem.MolFromSmiles(smiles)\n",
    "    if mol is None:\n",
    "        print(\"Failed to create molecule from SMILES\")\n",
    "        return None\n",
    "\n",
    "    mol = Chem.AddHs(mol)\n",
    "    params = AllChem.ETKDGv3()\n",
    "    params.randomSeed = 42\n",
    "    if not AllChem.EmbedMultipleConfs(mol, numConfs=num_confs, params=params):\n",
    "        print(\"Embedding conformations failed.\")\n",
    "        return None\n",
    "\n",
    "    results = []\n",
    "    for conf_id in range(num_confs):\n",
    "        ff = AllChem.MMFFGetMoleculeForceField(mol, AllChem.MMFFGetMoleculeProperties(mol), confId=conf_id)\n",
    "        if ff is None:\n",
    "            print(f\"Failed to setup MMFF for conformer {conf_id}\")\n",
    "            continue\n",
    "        energy = ff.Minimize()\n",
    "        results.append((conf_id, ff.CalcEnergy()))\n",
    "\n",
    "    if not results:\n",
    "        print(\"No successful energy minimization.\")\n",
    "        return None\n",
    "    \n",
    "\n",
    "    best_conf = mol.GetConformer(min_energy_conf[0])\n",
    "    best_mol = Chem.Mol(mol)\n",
    "    best_mol.RemoveAllConformers()\n",
    "    best_mol.AddConformer(best_conf, assignId=True)\n",
    "\n",
    "    coords = best_conf.GetPositions()\n",
    "    atom_symbols = [atom.GetSymbol() for atom in best_mol.GetAtoms()]\n",
    "    geometry = '\\n'.join(f'{atom} {coord[0]} {coord[1]} {coord[2]}' for atom, coord in zip(atom_symbols, coords))\n",
    "\n",
    "    display (best_mol)\n",
    "    \n",
    "    return geometry, best_mol"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "23f18039-4441-496c-89b0-9e467eaac83e",
   "metadata": {},
   "source": [
    "### Property calculation as possible starting point for design iterations "
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "id": "6519474d-4e03-4273-a79e-454d5845e6d6",
   "metadata": {
    "scrolled": true
   },
   "outputs": [],
   "source": [
    "SMILES_START='O1C2C3OC2C13'\n",
    "properties,_=avg_properties_from_SMILES (model, tokenizer, SMILES_START, SMILES_dir=SMILES_dir,\n",
    "                                temperature=0.3, top_k=256,top_p=0.9, num_beams=1,   repetition_penalty=1.,\n",
    "                                labels=labels, N_prop=3, plot_results=True)\n"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "id": "198840ea-21f8-41eb-b62a-bc325261b731",
   "metadata": {},
   "outputs": [],
   "source": [
    "# Retrieve the scaling parameters\n",
    "data_min = scaler.data_min_\n",
    "data_max = scaler.data_max_\n",
    "scale = scaler.scale_\n",
    "feature_min = scaler.min_\n",
    "\n",
    "print(\"Feature Scaling Parameters:\")\n",
    "print(\"{:<20} {:<20} {:<20} {:<20}\".format(\"Feature Index\", \"Min Value\", \"Max Value\", \"Scale Factor\"))\n",
    "for i in range(len(data_min)):\n",
    "    print(\"{:<20} {:<20} {:<20} {:<20}\".format(i, data_min[i], data_max[i], scale[i]))\n",
    "\n",
    "print(\"\\nPer-feature Shifts (Min):\")\n",
    "for i, min_val in enumerate(feature_min):\n",
    "    print(\"Feature {}: {:.6f}\".format(i, min_val))"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "0dd1f217-74c0-40f3-8edc-4b610c12e0ea",
   "metadata": {},
   "source": [
    "### Molecular design: Iterative solution "
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "id": "fc2747b6-90cc-4d42-bf93-bb39dc6d9198",
   "metadata": {},
   "outputs": [],
   "source": [
    "import copy \n",
    "properties=y_test[4]\n",
    "\n",
    "#Create new set of properties based on existing molecule (from test set)\n",
    "properties_new=copy.deepcopy (properties)\n",
    "properties_new[0]=properties[0]+0.2\n",
    "properties_new[1]=properties[1]+0.2\n",
    "plot_change_in_design (properties, labels, properties_new,SMILES_dir)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "id": "c5f9b9c5-c746-48d1-841a-a2113d13279e",
   "metadata": {
    "scrolled": true
   },
   "outputs": [],
   "source": [
    "df_design=design_molecule_loop (model, tokenizer, np.array(properties_new), SMILES_LIST=SMILES_LIST, dir_path=SMILES_dir,\n",
    "                          temperature_pred=0.1, temperature_gen=0.3, top_k=32,top_p=0.1,    repetition_penalty=1.,\n",
    "                         threshold=0.001, N_max=64,  \n",
    "                                N_attempts_for_forward=6,\n",
    "                               )"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "id": "8c5be323-aa47-49dd-bc44-be74936c62c8",
   "metadata": {
    "scrolled": true
   },
   "outputs": [],
   "source": [
    "visualize_over_SMILES (df_design,N_max=30,SMILES_dir=SMILES_dir,per_row=5,\n",
    "            lower_bound = 0.0, remove_duplicates=True,\n",
    "            upper_bound = 0.02, target=np.array(properties_new))\n",
    "\n",
    "target=np.array(properties_new)\n",
    "best_SMILES, best_predicted, best_mse, is_novel = df_design_2.iloc[5]\n",
    "\n",
    "print (\"Best SILES: \", best_SMILES)\n",
    "print (f\"{best_SMILES} is novel: {is_novel}\")\n",
    "\n",
    "sns.set_style(\"whitegrid\")\n",
    "\n",
    "visualize_pred_vs_target (target, best_predicted, labels, dir_path=SMILES_dir, best_SMILES=best_SMILES,sample_count=0)\n",
    " \n",
    "visualize_SMILES(best_SMILES, dir_path=SMILES_dir, root=f'{target}_BEST')"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "id": "25fd7dbe-95fd-4169-86e9-b05e86bbfb3a",
   "metadata": {
    "scrolled": true
   },
   "outputs": [],
   "source": [
    "target=np.array(properties_new)\n",
    "best_SMILES, best_predicted, best_mse, is_novel = df_design_2.iloc[5]\n",
    "\n",
    "print (\"Best SILES: \", best_SMILES)\n",
    "print (f\"{best_SMILES} is novel: {is_novel}\")\n",
    "\n",
    "sns.set_style(\"whitegrid\")\n",
    "\n",
    "visualize_pred_vs_target (target, best_predicted, labels, dir_path=SMILES_dir, best_SMILES=best_SMILES,sample_count=0)\n",
    " \n",
    "visualize_SMILES(best_SMILES, dir_path=SMILES_dir, root=f'{target}_BEST')"
   ]
  }
 ],
 "metadata": {
  "environment": {
   "kernel": "python3",
   "name": ".m115",
   "type": "gcloud",
   "uri": "gcr.io/deeplearning-platform-release/:m115"
  },
  "kernelspec": {
   "display_name": "Python 3 (ipykernel)",
   "language": "python",
   "name": "python3"
  },
  "language_info": {
   "codemirror_mode": {
    "name": "ipython",
    "version": 3
   },
   "file_extension": ".py",
   "mimetype": "text/x-python",
   "name": "python",
   "nbconvert_exporter": "python",
   "pygments_lexer": "ipython3",
   "version": "3.11.7"
  }
 },
 "nbformat": 4,
 "nbformat_minor": 5
}