Cavasotto Claudio N, Orry Andrew J W
MolSoft LLC, 3366 North Torrey Pines Ct. #300, La Jolla, CA 92037, USA.
Curr Top Med Chem. 2007;7(10):1006-14. doi: 10.2174/156802607780906753.
Ligand-docking-based methods are starting to play a critical role in lead discovery and optimization, thus resulting in new 'drug-candidates'. They offer the possibility to go beyond the pool of existing active compounds, and thus find novel chemotypes. A brief tutorial on ligand docking and structure-based virtual screening is presented highlighting current problems and limitations, together with the most recent methodological and algorithmic developments in the field. Recent successful applications of docking-based tools for hit discovery, lead optimization and target-biased library design are also presented. Special consideration is devoted to ongoing efforts to account for protein flexibility in structure-based virtual screening.
基于配体对接的方法在先导化合物发现和优化中开始发挥关键作用，从而产生新的“候选药物”。它们提供了超越现有活性化合物库的可能性，进而发现新型化学结构类型。本文简要介绍了配体对接和基于结构的虚拟筛选，强调了当前存在的问题和局限性，以及该领域最新的方法和算法进展。还介绍了基于对接的工具在命中发现、先导化合物优化和靶向文库设计方面的近期成功应用。特别关注了在基于结构的虚拟筛选中考虑蛋白质柔性的持续努力。
