Probing the interaction of HAV4 peptide (Ac-SHAVAS-NH2) with E-cadherin domain EC1-EC2 by molecular docking

Abstract

E-cadherin-derived peptides, which are peptide sequences taken from their binding sites, have been shown to be able to modulate cross-cell junction so as to facilitate drug delivery to their targets. One of the E-cadherin-derived peptides, HAV4 (Ac-SHAVAS-NH2) previously has been studied by in vitro and in vivo where the activity of the HAV4 peptide is able to modulate the tight junction between E-cadherin cells. The physicochemical properties of macromolecule such as protein or peptide are very important to understand the function of the macromolecule. Computational chemistry method has good advantage for understanding physicochemical properties in studying the structure, dynamic, and interaction of molecules in support of experimental data. The purpose of this study is to prove the inhibitory activity of interaction between E-cadherin cells and the best conformation of HAV4 peptide by its binding energy and active site parameters. This study uses molecular dynamic simulation and molecular docking. The results of research in 27°C temperature at 20000 ps molecular dynamic simulation which prove the HAV4 peptide has the best conformation at the 2508 ps with conformation energy -47704.4 kJ.mol−1. Based on the results of molecular docking simulation, interaction between HAV4 peptide and E-cadherin domain EC1-EC2 show binding energy of -24.393 kJ.mol−1 with the Ki inhibition constant of 53.17 µM. This strong interaction occurs in the adhesion arm-acceptor pocket area with residual active sites Trp2, Ile4, Ile24, Lys25, Ser26, Asn27, Ser78, Glu89, Asp90, Met92.