Alaofi Ahmed, Farokhi Elinaz, Prasasty Vivitri D, Anbanandam Asokan, Kuczera Krzysztof, Siahaan Teruna J
a Department of Pharmaceutical Chemistry , The University of Kansas , 2095 Constant Avenue, Lawrence , KS 66047 , USA.
d Faculty of Biotechnology , Atma Jaya Catholic University of Indonesia , Jakarta 12930 , Indonesia.
J Biomol Struct Dyn. 2017 Jan;35(1):92-104. doi: 10.1080/07391102.2015.1133321. Epub 2016 Apr 12.
The goal of this work is to probe the interaction between cyclic cHAVc3 peptide and the EC1 domain of human E-cadherin protein. Cyclic cHAVc3 peptide (cyclo(1,6)Ac-CSHAVC-NH) binds to the EC1 domain as shown by chemical shift perturbations in the 2D H,-N-HSQC NMR spectrum. The molecular dynamics (MD) simulations of the EC1 domain showed folding of the C-terminal tail region into the main head region of the EC1 domain. For cHAVc3 peptide, replica exchange molecular dynamics (REMD) simulations generated five structural clusters of cHAVc3 peptide. Representative structures of cHAVc3 and the EC1 structure from MD simulations were used in molecular docking experiments with NMR constraints to determine the binding site of the peptide on EC1. The results suggest that cHAVc3 binds to EC1 around residues Y36, S37, I38, I53, F77, S78, H79, and I94. The dissociation constants (K values) of cHAVc3 peptide to EC1 were estimated using the NMR chemical shifts data and the estimated Ks are in the range of .5 × 10-7.0 × 10 M.
这项工作的目标是探究环状cHAVc3肽与人E-钙黏蛋白的EC1结构域之间的相互作用。二维1H-N-HSQC NMR谱中的化学位移扰动表明，环状cHAVc3肽（环(1,6)Ac-CSHAVC-NH）与EC1结构域结合。EC1结构域的分子动力学（MD）模拟显示，C末端尾部区域折叠到EC1结构域的主要头部区域。对于cHAVc3肽，副本交换分子动力学（REMD）模拟生成了cHAVc3肽的五个结构簇。MD模拟得到的cHAVc3的代表性结构和EC1结构用于带有NMR约束的分子对接实验，以确定该肽在EC1上的结合位点。结果表明，cHAVc3在Y36、S37、I38、I53、F77、S78、H79和I94等残基周围与EC1结合。利用NMR化学位移数据估算了cHAVc3肽与EC1的解离常数（K值），估算的Ks在0.5×10⁻⁷ - 7.0×10⁻⁶ M范围内。
