Probing the interaction between EC1-EC2 domain of E-cadherin with conformational structure of cyclic ADTC7 (Ac-CDTPDC-NH2) peptide using molecular docking approach

Abstract

Abstract Increasing significantly brain disease every year make difficult to help people who suffer disease in their brain. Drug delivery can be reached through a paracellular pathway. The use of the derivative cadherin peptides (ADT and HAV) to enhance the porosity in this pathway was investigated. The aim of this studied to determine the best conformation of cyclic ADTC7 peptide which interacts with EC1-EC2 domain of E-cadherin with energy binding and active sites parameters. The methods used in this study are: 1). MD simulation using GROMACS software, and 2). Molecular docking with AutoDock software. The variation used on MD simulation are atomic distances and constant restrains in atom S14…S78 for 20 ns. The result of MD simulation for 20 ns shows that the linear and cyclic ADTC7 peptide are -118,824.84 kJ.mol−1 and -52,985.95 kJ.mol−1, respectively. The best conformation of cyclic ADTC7 peptide with the EC1-EC2 domain of E-cadherin is C1 with the lowest binding energy of -24.56 kJmol-1. The active site at residues such as Val3, Ile4, Pro5, Pro6, Ile7, Ser8, Leu21, Val22, Gln23, Lys25. It has RMSD value less than 2 Å, low energy binding and low inhibition constant, a large population and a stable pose when validation docking.