Energy-entropy method using multiscale cell correlation to calculate binding free energies in the SAMPL8 host-guest challenge.
Energy-entropy method using multiscale cell correlation to calculate binding free energies in the SAMPL8 host-guest challenge.
复制标题
能量熵方法使用多尺度细胞相关性来计算SAMPL8主客体挑战中的结合自由能。
DOI：
10.1007/s10822-021-00406-5
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发表时间：
2021-08
影响因子：
3.5
通讯作者：
Henchman RH
中科院分区：
文献类型：
--
作者：
Ali HS;Chakravorty A;Kalayan J;de Visser SP;Henchman RH
自由能驱动广泛的分子过程，如溶剂化、结合、化学反应和构象变化。考虑到结合的核心重要性，存在各种各样的方法来计算它，无论是基于评分函数，机器学习，经典或电子结构方法，炼金术，还是能量和熵的显式评估。本文提出了一种新的能量熵方法，直接从分子动力学模拟中计算主客体结合自由能。使用多尺度细胞相关性（MCC）评估熵，MCC使用力和扭矩协方差以及两个不同长度尺度的接触。该方法在SAMPL 8（蛋白质和配体建模的统计评估）“滥用药物”盲法挑战中对一系列七种主客体复合物进行了测试。EE-MCC结合自由能与实验结果一致，平均误差为0.9 kcal mol−1。MCC明确了熵变的起源，表明每个结合客体的位置、取向和在较小程度上的构象熵的大损失由释放到本体的水的取向熵的增益补偿，结合主体、客体和接触水的振动熵的较小减小。在线版本包含补充材料，可通过10.1007/s10822-021-00406-5获得。
Free energy drives a wide range of molecular processes such as solvation, binding, chemical reactions and conformational change. Given the central importance of binding, a wide range of methods exist to calculate it, whether based on scoring functions, machine-learning, classical or electronic structure methods, alchemy, or explicit evaluation of energy and entropy. Here we present a new energy–entropy (EE) method to calculate the host–guest binding free energy directly from molecular dynamics (MD) simulation. Entropy is evaluated using Multiscale Cell Correlation (MCC) which uses force and torque covariance and contacts at two different length scales. The method is tested on a series of seven host–guest complexes in the SAMPL8 (Statistical Assessment of the Modeling of Proteins and Ligands) “Drugs of Abuse” Blind Challenge. The EE-MCC binding free energies are found to agree with experiment with an average error of 0.9 kcal mol−1. MCC makes clear the origin of the entropy changes, showing that the large loss of positional, orientational, and to a lesser extent conformational entropy of each binding guest is compensated for by a gain in orientational entropy of water released to bulk, combined with smaller decreases in vibrational entropy of the host, guest and contacting water. The online version contains supplementary material available at 10.1007/s10822-021-00406-5.
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影响因子：
15
作者：
Abel, Robert;Young, Tom;Friesner, Richard A.
通讯作者：
Friesner, Richard A.
DOI：
10.3390/e21080750
发表时间：
2019-07-31
期刊：
Entropy (Basel, Switzerland)
影响因子：
--
作者：
Ali HS;Higham J;Henchman RH
通讯作者：
Henchman RH
影响因子：
3.4
作者：
Irudayam, Sheeba Jem;Plumb, Richard D.;Henchman, Richard H.
通讯作者：
Henchman, Richard H.
影响因子：
15
作者：
Gervasio, FL;Laio, A;Parrinello, M
通讯作者：
Parrinello, M
影响因子：
15
作者：
Chang, CE;Gilson, MK
通讯作者：
Gilson, MK