Computational Drug Design Accommodating Receptor Flexibility: The Relaxed Complex Scheme

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• 作者：Jung-Hsin Lin ; Alexander L. Perryman ; Julie R. Schames ; and J. Andrew McCammon
• 刊名：Journal of the American Chemical Society
• 出版年：2002
• 出版时间：May 22, 2002
• 年：2002
• 卷：124
• 期：20
• 页码：5632 - 5633
• 全文大小：150K
• 年卷期：v.124,no.20(May 22, 2002)
• ISSN：1520-5126

文摘

A novel computational methodology for drug design that accommodates receptor flexibility is described. This "relaxed-complex" method recognizes that ligand may bind to conformations that occur only rarely in the dynamics of the receptor. We have shown that the ligand-enzyme binding modes are very sensitive to the enzyme conformations, and our approach is capable of finding the best ligand-enzyme complexes. This new method serves as the computational analog of the experimental "SAR by NMR" and "tether" methods, which permit a building block approach for constructing a very potent drug.