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使用基于片段分子轨道的密度泛函紧束缚方法快速准确评估GPCR-配体相互作用

Rapid and accurate assessment of GPCR-ligand interactions Using the fragment molecular orbital-based density-functional tight-binding method.

作者信息

Morao Inaki, Fedorov Dmitri G, Robinson Roger, Southey Michelle, Townsend-Nicholson Andrea, Bodkin Mike J, Heifetz Alexander

机构信息

Computational Chemistry, Evotec (UK) Ltd, 114 Innovation Drive, Milton Park, Abingdon, Oxfordshire, OX14 4RZ, United Kingdom.

Research Center for Computational Design of Advanced Functional Materials (CD-FMat), National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Umezono, Tsukuba, Ibaraki, 305-8568, Japan.

出版信息

J Comput Chem. 2017 Sep 5;38(23):1987-1990. doi: 10.1002/jcc.24850. Epub 2017 Jul 4.

DOI:10.1002/jcc.24850
PMID:28675443
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5600120/
Abstract

The reliable and precise evaluation of receptor-ligand interactions and pair-interaction energy is an essential element of rational drug design. While quantum mechanical (QM) methods have been a promising means by which to achieve this, traditional QM is not applicable for large biological systems due to its high computational cost. Here, the fragment molecular orbital (FMO) method has been used to accelerate QM calculations, and by combining FMO with the density-functional tight-binding (DFTB) method we are able to decrease computational cost 1000 times, achieving results in seconds, instead of hours. We have applied FMO-DFTB to three different GPCR-ligand systems. Our results correlate well with site directed mutagenesis data and findings presented in the published literature, demonstrating that FMO-DFTB is a rapid and accurate means of GPCR-ligand interactions. © 2017 Authors. Journal of Computational Chemistry Published by Wiley Periodicals, Inc.

摘要

受体-配体相互作用和配对相互作用能的可靠且精确评估是合理药物设计的关键要素。虽然量子力学（QM）方法一直是实现这一目标的一种有前景的手段，但传统QM因其高计算成本而不适用于大型生物系统。在此，片段分子轨道（FMO）方法已被用于加速QM计算，并且通过将FMO与密度泛函紧束缚（DFTB）方法相结合，我们能够将计算成本降低1000倍，在数秒而非数小时内获得结果。我们已将FMO-DFTB应用于三种不同的GPCR-配体系统。我们的结果与定点诱变数据以及已发表文献中的发现高度相关，表明FMO-DFTB是一种快速且准确的GPCR-配体相互作用研究方法。© 2017作者。《计算化学杂志》由威利期刊公司出版

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa25/5600120/3ff383c196a2/JCC-38-1987-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa25/5600120/53cebbe65cb3/JCC-38-1987-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa25/5600120/353596a3486a/JCC-38-1987-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa25/5600120/3ff383c196a2/JCC-38-1987-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa25/5600120/53cebbe65cb3/JCC-38-1987-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa25/5600120/353596a3486a/JCC-38-1987-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa25/5600120/3ff383c196a2/JCC-38-1987-g003.jpg

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