Расчет квантово-химических параметров ФАВ и определение зависимости "структура-активность" на примере сульфаниламидов (стр. 18 из 19)
| Угол | Abinitio (минимальный базис), 0 | INDO, 0 | АМ1, 0 | Эксперимент |
| 23-13-22 | 117,425 | 109,843 | 112,842 | 117,582 |
| 23-13-12 | 120,172 | 117,345 | 116,154 | 120,547 |
| 24-14-12 | 117,522 | 116,284 | 116,731 | 117,365 |
| 14-12-11 | 118,567 | 123,237 | 115,637 | 118,359 |
| 3-8-11 | 97,213 | 94,305 | 97,6621 | 97,5 |
| 10-8-9 | 120,732 | 137,499 | 118,173 | 120,489 |
| 20-7-19 | 117,818 | 109,349 | 116,758 | 117,236 |
| 2-3-8 | 119,744 | 116,999 | 120,919 | 119,748 |
| 10-8-11 | 112,587 | 108,694 | 111,474 | 112,589 |
| 9-8-11 | 109 | 101,344 | 110,963 | 109,426 |
Рассчитанные молекулярные свойства сульгина методом АМ1
Полнаяэнергия: -62175,125
Binding energy: -2372,508
Heat of formation: -17,7407
Electronic energy: 328239,375
Nuclear energy: 266064,25
Дипольныймомент: 7,814
RMS градиент: 0,09855
Градиент X: 0,04252
Градиент Y: 0,05513
Градиент Z: 0,06976
| 25 Substructure descriptors; 2 new. |
| 38 Possible activities at Pa > 50% |
| Pa Pi Activity: |
| 0,947 0,008 Hematotoxic |
| 0,930 0,005 Antiprotozoal (Toxoplasma) |
| 0,926 0,003 Dihydropteroate synthase inhibitor |
| 0,900 0,003 Para amino benzoic acid antagonist |
| 0,863 0,005 Pyruvate kinase inhibitor |
| 0,797 0,019 Integrin antagonist |
| 0,769 0,008 Cathepsin G inhibitor |
| 0,764 0,004 Adenylate kinase inhibitor |
| 0,759 0,007 Prostaglandin H2 antagonist |
| 0,751 0,006 Prostaglandin E1 antagonist |
| 0,751 0,018 Insulinotropin agonist |
| 0,738 0,007 Gingipain K inhibitor |
| 0,723 0,007 Antianginal |
| 0,695 0,006 6 Phosphofructokinase inhibitor |
| 0,679 0,008 Corticotropin releasing factor antagonist |
| 0,669 0,004 Gingipain R inhibitor |
| 0,692 0,046 Dopamine D4 agonist |
| 0,672 0,036 Antineoplastic (colorectal cancer) |
| 0,627 0,007 GABA aminotransferase inhibitor |
| 0,641 0,028 Thiol oxidase inhibitor |
| 0,622 0,019 Diamine N-acetyltransferase inhibitor |
| 0,617 0,018 Muscular dystrophy treatment |
| 0,623 0,026 Cyclooxygenase 1 inhibitor |
| 0,607 0,011 Channel-conductance-controlling ATPase inhibitor |
| 0,612 0,026 Insulysin inhibitor |
| 0,631 0,048 Antineoplastic (brain cancer) |
| 0,577 0,003 Sulfonylureas |
| 0,579 0,018 Legumain inhibitor |
| 0,575 0,021 Cytochrome P450 CYP2C9 inhibitor |
| 0,617 0,071 Antinephritic |
| 0,546 0,014 Gamma-glutamyltransferase inhibitor |
| 0,536 0,021 Platelet adhesion inhibitor |
| 0,520 0,007 Loop diuretic |
| 0,580 0,069 Laccase inhibitor |
| 0,514 0,018 Subtilisin inhibitor |
| 0,506 0,012 CYP2C10 substrate |
| 0,533 0,045 Antiinflammatory, intestinal |
Приложение Д
Рис. Д.1 Молекула в abinitioРис. Д.2 Молекула в AM1
Таблица Д.1 Рассчитанные длины связей сульфадимезина
| Связь | Abinitio (минимальный базис), А | INDO, А | АМ1, А | Эксперимент |
| 13-28 | 0,995721 | 1,06838 | 0,990704 | 0,99428 |
| 13-27 | 0,995756 | 1,06829 | 0,990582 | 0,99568 |
| 13-12 | 1,36092 | 1,39286 | 1,37716 | 1,3546 |
| 12-11 | 1,40248 | 1,40007 | 1,42207 | 1,4058 |
| 11-10 | 1,37187 | 1,38653 | 1,38142 | 1,37259 |
| 10-9 | 1,3781 | 1,37635 | 1,40498 | 1,37126 |
| 9-8 | 1,37658 | 1,37697 | 1,40326 | 1,37658 |
| 8-7 | 1,37317 | 1,3858 | 1,38353 | 1,37248 |
| 7-12 | 1,40056 | 1,40006 | 1,42035 | 1,40 |
| 9-14 | 1,7833 | 1,91971 | 1,65908 | 1,7654 |
| 14-6 | 1,58452 | 1,90898 | 1,40135 | 1,58624 |
| 14-15 | 1,57749 | 1,93554 | 1,41607 | 1,5778 |
| 14-16 | 1,69873 | 1,85885 | 1,65696 | 1,70 |
| 16-17 | 1,3929 | 1,38514 | 1,0325 | 1,3944 |
| 17-5 | 1,34898 | 1,36903 | 1,3843 | 1,3426 |
| 5-1 | 1,47709 | 1,42733 | 1,35295 | 1,47256 |
| 1-2 | 1,51535 | 1,46651 | 1,41031 | 1,51248 |
| 2-3 | 1,32317 | 1,35116 | 1,41124 | 1,326 |
| 3-4 | 1,41485 | 1,4025 | 1,35223 | 1,418 |
| 4-17 | 1,27411 | 1,32434 | 1,38645 | 1,27562 |
| 1-18 | 1,54175 | 1,47571 | 1,49513 | 1,5487 |
| 3-19 | 1,50349 | 1,45993 | 1,49541 | 1,5032 |
Таблица Д.2 Рассчитанные валентные углы сульфадимезина
| Угол | Abinitio (минимальный базис), 0 | INDO, 0 | АМ1, 0 | Эксперимент |
| 28-13-27 | 117,792 | 109,473 | 117,054 | 117,268 |
| 1-5-17 | 120,779 | 121,345 | 116,376 | 120,236 |
| 3-4-17 | 116,995 | 112,797 | 116,189 | 116,154 |
| 4-17-16 | 116,952 | 113,257 | 118,041 | 117 |
| 6-14-15 | 120,536 | 135,83 | 115,761 | 120,125 |
| 9-14-6 | 107,391 | 101,842 | 110,818 | 107,487 |
| 9-14-15 | 109,827 | 105,593 | 108,935 | 109,625 |
| 18-1-5 | 110,248 | 112,22 | 118,79 | 110,587 |
| 19-3-4 | 113,301 | 112,277 | 118,769 | 113,246 |
| 8-9-14 | 119,532 | 115,273 | 121,676 | 119,326 |
Рассчитанные молекулярные свойства сульфадимезина методом АМ1
Полнаяэнергия: -78205,17969
Binding energy: 3420,6650
Heat of formation: -3,0390
Electronic energy: -497884,4375
Nuclear energy: 419679,25
Дипольныймомент: 7,099
RMS градиент: 0,09731
Градиент X: 0,05463
Градиент Y: 0,06094
Градиент Z: 0,05265
| 29 Substructure descriptors; 0 new. |
| Antibacterial |
| Teratogen |
| Carcinogenic |
| Antibiotic |
| Carcinogenic, group 3 |
| Carcinogenic, female rats |
| Carcinogenic, male rats |
| CYP2 substrate |
| Carcinogenic, female mice |
| Carcinogenic, male mice |
| CYP3A substrate |
| CYP2B substrate |
| CYP1A substrate |
| CYP1A1 substrate |
| CYP2C substrate |
| CYP2C11 substrate |
| Diamine N-acetyltransferase inhibitor |
| 28 Possible activities at Pa > 50% |
| Pa Pi Activity: |
| 0,970 0,002 Antiprotozoal (Toxoplasma) |
| 0,938 0,002 Dihydropteroate synthase inhibitor |
| 0,881 0,004 Para amino benzoic acid antagonist |
| 0,791 0,049 Hematotoxic |
| 0,758 0,018 Antineoplastic (colorectal cancer) |
| 0,795 0,073 Prolyl aminopeptidase inhibitor |
| 0,708 0,041 Dopamine D4 agonist |
| 0,699 0,032 Antineoplastic (brain cancer) |
| 0,677 0,029 Torsades de pointes |
| 0,656 0,041 Oxidoreductase inhibitor |
| 0,621 0,015 Prostaglandin H2 antagonist |
| 0,616 0,011 Cytochrome P450 CYP2C9 inhibitor |
| 0,651 0,055 Arrhythmogenic |
| 0,635 0,042 Laccase inhibitor |
| 0,598 0,020 Antiviral (Picornavirus) |
| 0,599 0,037 Thiol oxidase inhibitor |
| 0,575 0,048 Cathepsin G inhibitor |
| 0,569 0,044 Gingipain K inhibitor |
| 0,536 0,012 Antidiabetic |
| 0,558 0,037 CYP3A2 substrate |
| 0,555 0,035 Antiinflammatory, intestinal |
| 0,506 0,006 HIV-1 integrase (3'-Processing) inhibitor |
| 0,505 0,025 Prostaglandin E1 antagonist |
| 0,514 0,036 Collagen inhibitor |
| 0,521 0,044 2,3-Dihydroxybenzoate 2,3-dioxygenase inhibitor |
| 0,529 0,059 Indole 2,3-dioxygenase inhibitor |
| 0,512 0,047 Cytochrome P450 inhibitor |
| 0,531 0,203 Antinephritic |
Рис. Е.1 Молекула в abinitio Рис. Е.2 Молекула в AM1
Таблица Е.1 Рассчитанные длины связей норсульфазола
| Связь | Abinitio (минимальный базис), А | INDO, А | АМ1, А | Эксперимент |
| 17-5 | 0,995612 | 1,06816 | 1,01 | 0,99548 |
| 18-5 | 0,995591 | 1,06802 | 0,990705 | 0,99256 |
| 5-11 | 1,3619 | 1,39326 | 1,3751 | 1,3678 |
| 11-10 | 1,40099 | 1,39976 | 1,42276 | 1,40 |
| 10-9 | 1,37268 | 1,38544 | 1,38203 | 1,37246 |
| 9-8 | 1,37763 | 1,37692 | 1,40647 | 1,3784 |
| 8-7 | 1,37757 | 1.37604 | 1,40339 | 1,37264 |
| 7-6 | 1,37246 | 1,38575 | 1,38213 | 1,37462 |
| 6-11 | 1,4015 | 1,40065 | 1,42028 | 1,40 |
| 8-12 | 1,78142 | 1,92024 | 1,65756 | 1,78154 |
| 12-13 | 1,57982 | 1,92757 | 1,41632 | 1,5793 |
| 12-4 | 1,56896 | 1,92859 | 1,39923 | 1,5624 |
| 12-14 | 1,72222 | 1,85325 | 1,66363 | 1,7236 |
| 14-23 | 1,00193 | 0,7051 | 0,996966 | 1,0 |
| 14-3 | 1,35648 | 1,36005 | 1,38039 | 1,3256 |
| 3-2 | 1,57071 | 1,29564 | 1,35162 | 1,5798 |
| 2-15 | 1,40382 | 1,39723 | 1.38194 | 1,4062 |
| 15-16 | 1,3282 | 1,32666 | 1,38272 | 1,3248 |
| 16-1 | 1,81343 | 1,86959 | 1,67758 | 1,8147 |
| 1-3 | 1,8234 | 1,89812 | 1,75158 | 1,8264 |
| 16-25 | 1,06327 | 1,10813 | 1,0868 | 1,048 |
| 15-24 | 1,06524 | 1,12019 | 1,09708 | 1,0367 |
Таблица Е.2 Рассчитанные валентные углы норсульфазола
| Угол | Abinitio (минимальный базис), 0 | INDO, 0 | АМ1, 0 | Эксперимент |
| 17-5-18 | 117,799 | 109,525 | 120,828 | 117,656 |
| 3-1-16 | 86,1528 | 83,1738 | 90,5661 | 86,236 |
| 1-16-15 | 110,184 | 110,015 | 110,73 | 110,489 |
| 1-3-2 | 114,61 | 116,952 | 113,303 | 114,324 |
| 13-12-4 | 119,801 | 134,681 | 116,045 | 119,648 |
| 8-12-13 | 108,518 | 104,832 | 109,187 | 108,659 |
| 8-12-4 | 110,647 | 107,433 | 111,139 | 110,487 |
| 12-14-3 | 124,669 | 114,056 | 127,536 | 124,357 |
| 14-3-2 | 125,248 | 134,195 | 124,775 | 125,2589 |
| 9-8-12 | 118,059 | 115,425 | 120,329 | 117,995 |
Рассчитанные молекулярные свойства норсульфазола методом АМ1
Полнаяэнергия: -67462,27344
Binding energy: -2596,3837
Heat of formation: 1,4622
Electronic energy: -381394,2813
Nuclear energy: 313932
Дипольныймомент: 0
RMS градиент: 0,30225
Градиент X: 0,17933
Градиент Y: 0,20430
Градиент Z: 0,13213
| 32 Substructure descriptors; 0 new. |
| Antibacterial |
| Antibiotic |
| Iodide peroxidase inhibitor |
| Dihydropteroate synthase inhibitor |
| 21 Possible activities at Pa > 50% |
| Pa Pi Activity: |
| 0,885 0,005 Antiobesity |
| 0,867 0,009 Antiprotozoal (Toxoplasma) |
| 0,834 0,006 Para amino benzoic acid antagonist |
| 0,785 0,020 Dopamine D4 agonist |
| 0,732 0,006 Dihydropteroate synthase inhibitor |
| 0,745 0,020 Antineoplastic (colorectal cancer) |
| 0,710 0,006 Antidiabetic |
| 0,673 0,038 Antineoplastic (brain cancer) |
| 0,688 0,079 Hematotoxic |
| 0,641 0,043 Antinephritic |
| 0,613 0,029 Cyclooxygenase 1 inhibitor |
| 0,579 0,019 Cytochrome P450 CYP2C9 inhibitor |
| 0,562 0,006 Antiprotozoal (Coccidial) |
| 0,549 0,020 Prostaglandin E1 antagonist |
| 0,562 0,042 Diamine N-acetyltransferase inhibitor |
| 0,541 0,026 Prostaglandin antagonist |
| 0,617 0,107 Mucomembranous protector |
| 0,503 0,026 Prostaglandin H2 antagonist |
| 0,488 0,017 CYP2C10 substrate |
| 0,507 0,041 Collagen inhibitor |
| 0,505 0,059 Antiinflammatory, intestinal |
Рис. Ж.1 Молекула в abinitio