Molecular dynamics simulation of the P2Y14 receptor.: Ligand docking and identification of a putative binding site of the distal hexose moiety
Molecular dynamics simulation of the P2Y14 receptor.: Ligand docking and identification of a putative binding site of the distal hexose moiety
复制标题
DOI：
10.1016/j.bmcl.2006.10.081
复制
发表时间：
2007-02-01
影响因子：
2.7
通讯作者：
Jacobson, Kenneth A.
中科院分区：
文献类型：
--
作者：
Ivanov, Andrei A.;Fricks, Ingrid;Jacobson, Kenneth A.
基于视紫红质的P2Y(14)受体同源模型被插入到磷脂双层中，并通过分子动力学(MD)模拟进行精炼。采用分子自动对接和蒙特卡罗多重极小计算相结合的方法，对几种已知的激动剂UDP-葡萄糖及其类似物的结合模式进行了研究。与其他P2Y受体相比，P2Y(14)受体具有非典型的碱基、核糖和磷酸部分的结合模式。二磷酸部分只与EL2的一个阳离子残基相互作用，而在其他P2Y受体亚型中，三个Arg或Lys残基与磷酸链相互作用。另外两个保守的阳离子残基，即P2Y(14)受体的Arg253(6.55)和Lys277(7.35)，以及两个阴离子残基(位于EL2的Glu166和Glul74)可能参与了与远端己糖部分的相互作用。(C)2006爱思唯尔有限公司。保留所有权利。
A rhodopsin-based homology model of the P2Y(14) receptor was inserted into a phospholipid bilayer and refined by molecular dynamics (MD) simulation. The binding modes of several known agonists, namely UDP-glucose and its analogues, were proposed using automatic molecular docking combined with Monte Carlo Multiple Minimum calculations. Compared to other P2Y receptors, the P2Y(14) receptor has an atypical binding mode of the nucleobase, ribose, and phosphate moieties. The diphosphate moiety interacts with only one cationic residue, namely Lys171 of EL2, while in other P2Y receptor subtypes three Arg or Lys residues interact with the phosphate chain. Two other conserved cationic residues, namely Arg253 (6.55) and Lys277 (7.35) of the P2Y(14) receptor together with two anionic residues (Glu166 and Glul74, located in EL2), are likely involved in interactions with the distal hexose moiety. (c) 2006 Elsevier Ltd. All rights reserved.