Docking ligands into flexible and solvated macromolecules. 1. Development and validation of FITTED 1.0
Docking ligands into flexible and solvated macromolecules. 1. Development and validation of FITTED 1.0
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DOI：
10.1021/ci6002637
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发表时间：
2007-03-01
影响因子：
5.6
通讯作者：
Moitessier, Nicolas
中科院分区：
文献类型：
--
作者：
Corbeil, Christopher R.;Englebienne, Pablo;Moitessier, Nicolas
我们报告的开发和验证的一套新的程序，FITTED 1.0，对接到灵活的蛋白质的灵活的配体。这种对接工具的独特之处在于，它可以处理大分子（侧链和主链）的灵活性和桥接水分子的存在，同时将蛋白质/配体复合物视为现实的动态系统。该软件依赖于遗传算法来解释两个分子的灵活性以及桥接水分子的位置。此外，FITTED 1.0还具有开关功能的新应用，以保留或取代蛋白质-配体复合物中的关键水分子。开发了两个独立的模块，ProCESS和SMART，以在对接阶段之前设置蛋白质和配体。通过将FITTED 1.0应用于HIV-1蛋白酶、胸苷激酶、胰蛋白酶、因子Xa和MMP的抑制剂与其各自蛋白质的对接，实现了软件准确性的验证。
We report the development and validation of a novel suite of programs, FITTED 1.0, for the docking of flexible ligands into flexible proteins. This docking tool is unique in that it can deal with both the flexibility of macromolecules (side chains and main chains) and the presence of bridging water molecules while treating protein/ligand complexes as realistically dynamic systems. This software relies on a genetic algorithm to account for the flexibility of the two molecules as well as the location of bridging water molecules. In addition, FITTED 1.0 features a novel application of a switching function to retain or displace key water molecules from the protein-ligand complexes. Two independent modules, ProCESS and SMART, were developed to set up the proteins and the ligands prior to the docking stage. Validation of the accuracy of the software was achieved via the application of FITTED 1.0 to the docking of inhibitors of HIV-1 protease, thymidine kinase, trypsin, factor Xa, and MMP to their respective proteins.