Interaction Entropy: A New Paradigm for Highly Efficient and Reliable Computation of Protein-Ligand Binding Free Energy
Interaction Entropy: A New Paradigm for Highly Efficient and Reliable Computation of Protein-Ligand Binding Free Energy
复制标题
相互作用熵：高效可靠计算蛋白质-配体结合自由能的新范式
DOI：
10.1021/jacs.6b02682
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发表时间：
2016-05-04
影响因子：
15
通讯作者：
Zhang, John Z. H.
中科院分区：
文献类型：
--
作者：
Duan, Lili;Liu, Xiao;Zhang, John Z. H.
高效可靠地计算蛋白质-配体结合自由能是计算生物学中的一个重大挑战，在药物设计和许多其他分子识别问题中至关重要。主要的挑战在于计算蛋白质-配体结合或相互作用系统的熵贡献。在这份报告中，我们提出了一个：新的相互作用熵方法，这是理论上严格的，计算效率高，数值上可靠的计算熵的贡献，在蛋白质配体结合和其他相互作用过程中的自由能。与目前广泛使用的计算蛋白质-配体结合熵变的标准模式方法不同，新方法直接从分子动力学模拟中计算结合自由能的熵分量（相互作用熵或- T Δ S），而不需要任何额外的计算费用。对十几个随机选择的蛋白质-配体结合系统的广泛研究表明，这种相互作用熵方法在计算上是有效的，数值上是可靠的，并且大大上级标准的正常模式方法。这种相互作用熵的范例介绍了一种新的和直观的概念性理解的熵效应在蛋白质-配体结合和其他一般的相互作用系统，以及一个实用的方法，高效地计算这种效果。
Efficient and reliable calculation of protein-ligand binding free energy is a grand challenge in computational biology and is of critical importance in drug design and many other molecular recognition problems. The main challenge lies in the calculation of entropic contribution to protein-ligand binding or interaction systems. In this report, we present a: new interaction entropy method which is theoretically rigorous, computationally efficient, and numerically reliable for calculating entropic contribution to free energy in protein-ligand binding and other interaction processes. Drastically different from, the widely employed but extremely expensive normal mode method for calculating entropy change in protein-ligand binding, the new method calculates the entropic component (interaction entropy or - T Delta S) of the binding free energy directly from molecular dynamics simulation without any extra computational cost. Extensive study of over a dozen randomly selected protein-ligand binding systems demonstrated that this interaction entropy method is both computationally efficient and numerically reliable and :is vastly superior to the standard normal mode approach. This interaction entropy paradigm introduces a novel and intuitive conceptual understanding of the entropic effect in protein-ligand binding and other general interaction systems as well as a practical method for highly efficient calculation of this effect.