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非锌螯合嘧啶二羧酰胺类基质金属蛋白酶-13（MMP-13）抑制剂结合自由能的计算

Calculation of binding free energies for non-zinc chelating pyrimidine dicarboxamide inhibitors with MMP-13.

作者信息

Carrascal Noel, Rizzo Robert C

机构信息

Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY 11794-3600, USA.

出版信息

Bioorg Med Chem Lett. 2009 Jan 1;19(1):47-50. doi: 10.1016/j.bmcl.2008.11.038. Epub 2008 Nov 18.

DOI:10.1016/j.bmcl.2008.11.038
PMID:19042129
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2646414/
Abstract

All-atom molecular dynamics (MD) simulations in both explicit and implicit solvent, followed by MM-GBSA energy analysis, have been used to estimate binding free energies of four pyrimidine dicarboxamide inhibitors with human collagenase-3 (MMP-13) for comparison with experimental activities. Energetic analysis reveals that affinity is driven primarily by favorable van der Waals interactions and burial of total surface area. The computed effects of desolvation, as a function of ligand structure, quantitatively show that hydrophilic derivatives pay greater penalties upon binding than their related more hydrophobic analogs.

摘要

在显式和隐式溶剂中进行全原子分子动力学（MD）模拟，随后进行MM-GBSA能量分析，以估计四种嘧啶二羧酰胺抑制剂与人胶原酶-3（MMP-13）的结合自由能，以便与实验活性进行比较。能量分析表明，亲和力主要由有利的范德华相互作用和总表面积的埋藏驱动。作为配体结构的函数计算出的去溶剂化效应定量表明，亲水性衍生物在结合时比其相关的疏水性更强的类似物受到更大的惩罚。

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