Probing of interaction mode between linier and cyclic ADTC6 (Ac-CDTPPC-NH2) with E-cadherin protein using molecular docking approach

13th Joint Conference on Chemistry

Siahaan, Parsaoran^1 ; Kaswanda, Jordy Armand^1 ; Budiyanto, Rikno^1 ; Darmastuti, Nur Esti^1 ; Hudiyanti, Dwi^1 ; Prasasty, Vivitri Dewi^2

Departement of Chemistry, Faculty of Science and Mathematics, Diponegoro University, Indonesia^1

Faculty of Biotechnology, Atma Jaya Catholic University of Indonesia, Indonesia^2

关键词: ADTC6;    Agrochemical industries;    E-cadherins;    Inhibition constants;    Intermolecular complexes;    Molecular docking;    Molecular dynamics simulations;    Peptide conformation;   

Others  :  https://iopscience.iop.org/article/10.1088/1757-899X/509/1/012108/pdf
DOI  :  10.1088/1757-899X/509/1/012108

来源: IOP

【 摘 要 】

Molecular modelling is a technique widely used to understand the properties and activity of molecules in the chemical, pharmaceutical and agrochemical industries. Modelling for macromolecule performed by force field method to find energy and the preferer conformation. Molecular docking method was applied to predict structure of the intermolecular complexes formed between two or more molecules. Molecular structures, dynamics and its interactions is important to determine and understand the function of macromolecule such as peptide or protein. In experimentally previous study the ADTC6 peptide was hypothesized to interact with E-cadherin which able to modify and increase the porosity of tight junction of cell. This study aims to prove the interaction between ADTC6 with E-cadherin and to determine the effect of ADTC6 peptide conformation on binding energy. The first step was the preparation and optimizing of linear and cyclic ADTC6 peptide molecules by molecular dynamics (MD) simulation method with GROMACS (Groningen Machine for Simulation) software. The simulation was done for 20 ns and 120 ns with definite distance parameters and constant restraints between S14 atom on Cys1 of ADTC6 and S78 atom on Cys6 of ADTC6. The second step was molecular docking between cyclic and linear ADTC6 with E-cadherin in EC1 domain. The result shows that binding energy was changed by different conformation. The lowest energy of linear ADTC6 by MD simulation for 20 ns was -60036.968 kJmol-1 (L6) with S14...S78 distance was 4.138 Å, and the cyclic was -51747.128 (S2) with S14...S78 distance was 2.029 Å. While the lowest energy of linear ADTC6 by MD simulation for 120 ns was -59838.9609 kJmol-1 and 17.674 Å. Docking simulation of ADTC6 peptide molecule ... E-cadherin EC1-EC2 domain shows ADTC6 peptide has strong binding energy in adhesion arm-acceptor pocket region compared to bulge-groove region. Cyclic ADTC6 peptide code S4 as the best conformation in interaction with E-cadherin EC1 because it has binding energy and low inhibition constants, a large population, and a stable pose when re-docking. The cyclic ADTC6 peptide binding energy in the adhesion arm-acceptor pocket region and bulge-groove region were -27.91 kJmol-1 and - 21.05 kJmol-1, respectively.