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- Title
The development of algorithm for pharmacophore model optimization and rescoring of pharmacophore screening results.
- Authors
Starosyla, S. A.; Volynets, G. P.; Protopopov, M. V.; Bdzhola, V. G.; Yarmoluk, S. M.
- Abstract
Pharmacophore modeling is modern efficient approach which is widely used in drug discovery. This method has several drawbacks. First of all, pharmacophore models are not selective to structurally similar compounds that belong to one chemical class but possess different activity. Another drawback is that during pharmacophore screening a number of non-active compounds can be selected in the top of results. We have developed novel algorithm for pharmacophore model optimization and for rescoring of pharmacophore screening results. The advantages of our algorithm are optimization of pharmacophore feature radii, application of the concept of pharmacophore feature weights and molecular descriptors. The algorithm was validated based on pharmacophore models of FGFR1 and CK2 inhibitors. In the case of FGFR1 pharmacophore model, the application of algorithm allowed to increase the number of active compounds identified during screening of validation set from 21 to 43 and percent of correctly found active compounds in the top was increased from 38 to 60%. In the case of CK2 pharmacophore model, the number of active compounds identified during screening of validation set increased from 12 to 39 and percent of correctly found active compounds in the top increased from 58 to 74%.
- Subjects
DRUG development; MEDICAL screening; DRUG efficacy; STRUCTURE-activity relationship in pharmacology; ALGORITHMS
- Publication
Ukrainica Bioorganica Acta, 2016, Vol 14, Issue 1, p24
- ISSN
1814-9758
- Publication type
Article