Precise force-field-based calculations of octanol-water partition coefficients for the SAMPL7 molecules.
Precise force-field-based calculations of octanol-water partition coefficients for the SAMPL7 molecules.
复制标题
DOI：
10.1007/s10822-021-00407-4
复制
发表时间：
2021-07
影响因子：
3.5
通讯作者：
Beckstein O
中科院分区：
文献类型：
--
作者：
Fan S;Nedev H;Vijayan R;Iorga BI;Beckstein O
我们预测的水-辛醇分配系数的分子在SAMPL 7的挑战与明确的溶剂经典分子动力学（MD）模拟。采用加窗炼金术自由能方法计算了水的水合自由能和辛醇的溶剂化自由能。测试了三种常用力场（AMBER GAFF、CHARMM CGenFF、OPLS-AA）。特别强调的是收敛所有的模拟，使用标准开发的SAMPL 6的挑战。总的来说，进行了超过1000 μs的模拟，即使在1 μs的模拟时间之后，一些自由能窗口仍然没有完全收敛。然而，采样量产生的logPow估计值的精度为0.1 log单位或更好的收敛模拟。尽管可能是尽可能充分的采样，可以预期和可行的，与实验的协议仍然温和的所有力场，没有力场表现优于1.6的均方根误差。总体而言，我们的研究结果表明，大量的采样是必要的，以产生精确的logPow预测的SAMPL 7化合物和高精度并不一定导致高准确度。因此，基于物理的logPow预测的基本问题仍然有待解决。
We predicted water-octanol partition coefficients for the molecules in the SAMPL7 challenge with explicit solvent classical molecular dynamics (MD) simulations. Water hydration free energies and octanol solvation free energies were calculated with a windowed alchemical free energy approach. Three commonly used force fields (AMBER GAFF, CHARMM CGenFF, OPLS-AA) were tested. Special emphasis was placed on converging all simulations, using a criterion developed for the SAMPL6 challenge. In aggregate, over 1000 μs of simulations were performed, with some free energy windows remaining not fully converged even after 1 μs of simulation time. Nevertheless, the amount of sampling produced logPow estimates with a precision of 0.1 log units or better for converged simulations. Despite being probably as fully sampled as can expected and is feasible, the agreement with experiment remained modest for all force fields, with no force field performing better than 1.6 in root mean squared error. Overall, our results indicate that a large amount of sampling is necessary to produce precise logPow predictions for the SAMPL7 compounds and that high precision does not necessarily lead to high accuracy. Thus, fundamental problems remain to be solved for physics-based logPow predictions.
登录
查看更多内容
影响因子：
5.5
作者：
Hess, Berk;Kutzner, Carsten;Lindahl, Erik
通讯作者：
Lindahl, Erik
影响因子：
3.5
作者：
Klimovich, Pavel V.;Shirts, Michael R.;Mobley, David L.
通讯作者：
Mobley, David L.
影响因子：
14.9
作者：
Dodda LS;Cabeza de Vaca I;Tirado-Rives J;Jorgensen WL
通讯作者：
Jorgensen WL
DOI：
10.1016/s0166-1280(97)00237-6
发表时间：
1998-02-09
期刊：
THEOCHEM-JOURNAL OF MOLECULAR STRUCTURE
影响因子：
--
作者：
Jorgensen, WL;McDonald, NA
通讯作者：
McDonald, NA
影响因子：
5.5
作者：
Hess, Berk
通讯作者：
Hess, Berk