Rapid parameterization of small molecules using the Force Field Toolkit.
Rapid parameterization of small molecules using the Force Field Toolkit.
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DOI：
10.1002/jcc.23422
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发表时间：
2013-12-15
影响因子：
3
通讯作者：
Gumbart, James C.
中科院分区：
文献类型：
--
作者：
Mayne, Christopher G.;Saam, Jan;Schulten, Klaus;Tajkhorshid, Emad;Gumbart, James C.
无法快速生成新化学物质的准确和鲁棒的参数继续严重限制了分子动力学（MD）模拟在许多感兴趣的生物系统中的应用，特别是在药物发现等领域。尽管常见经典力场的广义版本（例如，GAFF和CGenFF已经提出了小分子参数化的指导方针，但仍然存在许多技术挑战，阻碍了它们的大规模推广。本文所述的力场工具包（ffTK）通过算法和方法开发、繁琐且易出错的任务的自动化以及图形用户界面设计来最小化配体参数化的常见障碍。作为一个VMD插件分发，ffTK促进了一个清晰和有组织的工作流的遍历，从而产生一组完整的CHARMM兼容参数。提供了各种工具来生成量子力学目标数据，设置多维优化例程，并分析参数性能。使用ffTK为小测试组的分子开发的参数与现有CGenFF参数在再现纯溶剂性质的实验测量值（来自实验的<15%误差）和溶剂化自由能（来自实验的±0.5 kcal/mol）的能力方面相当。
The inability to rapidly generate accurate and robust parameters for novel chemical matter continues to severely limit the application of molecular dynamics (MD) simulations to many biological systems of interest, especially in fields such as drug discovery. Although the release of generalized versions of common classical force fields, e.g., GAFF and CGenFF, have posited guidelines for parameterization of small molecules, many technical challenges remain that have hampered their wide-scale extension. The Force Field Toolkit (ffTK), described herein, minimizes common barriers to ligand parameterization through algorithm and method development, automation of tedious and error-prone tasks, and graphical user interface design. Distributed as a VMD plugin, ffTK facilitates the traversal of a clear and organized workflow resulting in a complete set of CHARMM-compatible parameters. A variety of tools are provided to generate quantum mechanical target data, set up multidimensional optimization routines, and analyze parameter performance. Parameters developed for a small test set of molecules using ffTK were comparable to existing CGenFF parameters in their ability to reproduce experimentally measured values for pure-solvent properties (<15% error from experiment) and free energy of solvation (±0.5 kcal/mol from experiment).
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影响因子：
4.1
作者：
BENNETT, CH
通讯作者：
BENNETT, CH
DOI：
10.1021/jz101461d
发表时间：
2011
期刊：
The journal of physical chemistry letters
影响因子：
--
作者：
Jiang W;Hardy DJ;Phillips JC;Mackerell AD Jr;Schulten K;Roux B
通讯作者：
Roux B
影响因子：
5.4
作者：
Durrant JD;McCammon JA
通讯作者：
McCammon JA
影响因子：
4.4
作者：
JORGENSEN, WL;CHANDRASEKHAR, J;KLEIN, ML
通讯作者：
KLEIN, ML
影响因子：
3.3
作者：
Drew, Kurt L. M.;Baiman, Hakim;Reynisson, Johannes
通讯作者：
Reynisson, Johannes