Testing and validation of the Automated Topology Builder (ATB) version 2.0: prediction of hydration free enthalpies
Testing and validation of the Automated Topology Builder (ATB) version 2.0: prediction of hydration free enthalpies
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DOI：
10.1007/s10822-014-9713-7
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发表时间：
2014-03-01
影响因子：
3.5
通讯作者：
Mark, Alan E.
中科院分区：
文献类型：
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作者：
Koziara, Katarzyna B.;Stroet, Martin;Mark, Alan E.
为了测试和验证自动力场拓扑构建器和存储库（ATB;），使用热力学积分估计了一组214个药物样分子（包括形成SAMPL 4挑战的一部分的47个分子）的无水化的分子量，并与实验进行了比较。使用全自动协议进行计算，该协议在选择中间点时纳入了收敛和积分误差的动态分析。该系统的设计和实施使得在将分子提交至ATB之后，可以在没有人工干预的情况下获得无水化的凝胶。使用ATB 2.0拓扑结构，对于214个分子的完整集合的总体平均无符号误差（AUE）为6.7 kJ/mol，并且对于SAMPL 4内的分子为7.5 kJ/mol。均方根误差（RMSE）分别为9.5和10.0kJ/mol。然而，对于含有形成主要GROMOS力场的一部分的官能团的分子，AUE为3.4 kJ/mol，RMSE为4.0 kJ/mol。这表明可以进一步完善ATB基于无水化合物提供的参数。
To test and validate the Automated force field Topology Builder and Repository (ATB;) the hydration free enthalpies for a set of 214 drug-like molecules, including 47 molecules that form part of the SAMPL4 challenge have been estimated using thermodynamic integration and compared to experiment. The calculations were performed using a fully automated protocol that incorporated a dynamic analysis of the convergence and integration error in the selection of intermediate points. The system has been designed and implemented such that hydration free enthalpies can be obtained without manual intervention following the submission of a molecule to the ATB. The overall average unsigned error (AUE) using ATB 2.0 topologies for the complete set of 214 molecules was 6.7 kJ/mol and for molecules within the SAMPL4 7.5 kJ/mol. The root mean square error (RMSE) was 9.5 and 10.0 kJ/mol respectively. However, for molecules containing functional groups that form part of the main GROMOS force field the AUE was 3.4 kJ/mol and the RMSE was 4.0 kJ/mol. This suggests it will be possible to further refine the parameters provided by the ATB based on hydration free enthalpies.