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	Hydroxamate类抑制剂与MMP-3的结合自由能的计算; Binding Preferenceof Hydroxamate Inhibitors of the Matrix Metalloproteinase- 3
	Zhang W(章威) ; Hou TJ(侯廷军) ; Xu XJ(徐筱杰)
	2001
关键词	自由能微扰,MMP-3,Stromelysin-1,hydroxamate类抑制剂,慢增长,fixed width window growth free energy perturbation MMP-3 stromelysin-1 hydroxamate slow growth fixed width window growth
英文摘要	用自由能微扰方法(FEP)计算了两种hydroxamate类的抑制剂和MMP-3的相对结合自由能.在计算中,对于催化区的锌离子与其共价结合的配体(包括抑制剂和组氨酸)采用了键合的模型,抑制剂和周围配体的部分电荷的计算采用两步静电势收敛方法.自由能计算采用了慢增长(Slow growth)和固定窗口增长(Fixed width window growth)两种方法,并且在每次计算中都采用了双向采样(Double-wide sampling)的策略.两种方法计算得到的相对结合自由能都能和实验值很好的符合.同时从动力学模拟的得到的分子轨迹得到了抑制剂和受体之间相互作用模式,抑制剂的P1部分可以和受体的S1′口袋形成很强的范德华和疏水相互作用,P1上的苯环可以和Tyr223上的苯环形成较好的π键堆积相互作用.; Molecular dynamics (MD) and free energy perturbation (FEP) studies were carried out on two enzyme- inhibitor complex of human Matrix Metalloproteinase - 3 to obtain energy preference of the two inhibitors. We have developed a bonded model for the catalytic zinc center ( including histidine and hydroxamate inhibitor that coordinated with catalytic zinc), where the charge of this model was derived using a two - step electrostatic potential fitting. Both slow growth method and fixed width window growth method with double - wide sampling were used in our simulations, it reproduced the structure feature well and the calculated relative free energy made a good agreement with experimental result. MD trajectories gave the binding mode between MMP - 3 and hydroxamates, the P-1 subunit of the inhibitor made a good van der Wall's contacts with the receptor's S-1' substituent. In particular, the benzene ring on P-1 could form a staking interaction with the pi - face of Tyr223.; 国家自然科学基金; 国家自然科学基金; SCI(E); 中文核心期刊要目总览(PKU); 中国科学引文数据库(CSCD); 1; 12; 2116-2121; 59
语种	中文
出处	万方 ; SCI ; http://d.g.wanfangdata.com.cn/Periodical_hxxb200112015.aspx
出版者	化学学报
内容类型	其他
源URL	[http://hdl.handle.net/20.500.11897/78507]
专题	化学与分子工程学院
推荐引用方式 GB/T 7714	章威,侯廷军,徐筱杰. Hydroxamate类抑制剂与MMP-3的结合自由能的计算, Binding Preferenceof Hydroxamate Inhibitors of the Matrix Metalloproteinase- 3. 2001-01-01.

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