Identification of a minimal subset of receptor conformations for improved multiple conformation docking and two-step scoring
- Authors
- Yoon S; Welsh WJ
- Issue Date
- Jan-2004
- Publisher
- AMER CHEMICAL SOC
- Citation
- JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES, v.44, no.1, pp 88 - 96
- Pages
- 9
- Journal Title
- JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES
- Volume
- 44
- Number
- 1
- Start Page
- 88
- End Page
- 96
- URI
- https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/148990
- DOI
- 10.1021/ci0341619
- ISSN
- 0095-2338
1520-5142
- Abstract
- Docking and scoring are critical issues in virtual drug screening methods. Fast and reliable methods are required for the prediction of binding affinity especially when applied to a large library of compounds. The implementation of receptor flexibility and refinement of scoring functions for this purpose are extremely challenging in terms of computational speed. Here we propose a knowledge-based multiple-conformation docking method that efficiently accommodates receptor flexibility thus permitting reliable virtual screening of large compound libraries. Starting with a small number of active compounds, a preliminary docking operation is conducted on a large ensemble of receptor conformations to select the minimal subset of receptor conformations that provides a strong correlation between the experimental binding affinity (e.g., K-i, IC50) and the docking score. Only this subset is used for subsequent multiple-conformation docking of the entire data set of library (test) compounds. In conjunction with the multiple-conformation docking procedure, a two-step scoring scheme is employed by which the optimal scoring geometries obtained from the multiple-conformation docking are re-scored by a molecular mechanics energy function including desolvation terms. To demonstrate the feasibility of this approach, we applied thi
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