6 5 2 1 2 g
Home About us MoEF Contact us Sitemap Tamil Website  
About Envis
Whats New
Research on Microbes
Microbiology Experts
Online Submission
Access Statistics

Site Visitors

blog tracking

Journal of Molecular Graphics and Modelling
Vol. 62, 2015, Pages: 138–149

Elucidation of the binding mechanism of renin using a wide array of computational techniques and biological assays

Haralambos Tzoupis, Georgios Leonis, Aggelos Avramopoulos, Heribert Reis, Zaneta Czyznikowska, Sofia Zerva, Niki Vergadou, Loukas D. Peristeras, Konstantinos D. Papavasileiou, Michael N. Alexis, Thomas Mavromoustakos, Manthos G. Papadopoulos

Institute of Biology, Pharmaceutical Chemistry and Biotechnology, National Hellenic Research Foundation, 48 Vas. Constantinou Ave., Athens 11635, Greece.


We investigate the binding mechanism in renin complexes, involving three drugs (remikiren, zankiren and enalkiren) and one lead compound, which was selected after screening the ZINC database. For this purpose, we used ab initio methods (the effective fragment potential, the variational perturbation theory, the energy decomposition analysis, the atoms-in-molecules), docking, molecular dynamics, and the MM-PBSA method. A biological assay for the lead compound has been performed to validate the theoretical findings. Importantly, binding free energy calculations for the three drug complexes are within 3 kcal/mol of the experimental values, thus further justifying our computational protocol, which has been validated through previous studies on 11 drug-protein systems. The main elements of the discovered mechanism are: (i) minor changes are induced to renin upon drug binding, (ii) the three drugs form an extensive network of hydrogen bonds with renin, whilst the lead compound presented diminished interactions, (iii) ligand binding in all complexes is driven by favorable van der Waals interactions and the nonpolar contribution to solvation, while the lead compound is associated with diminished van der Waals interactions compared to the drug-bound forms of renin, and (iv) the environment (H2O/Na+) has a small effect on the renin–remikiren interaction.

Graphical abstract

Keywords: Renin; Molecular dynamics; Ab initio calculations; Free energy calculations.

Copyright © 2005 ENVIS Centre ! All rights reserved
This site is optimized for 1024 x 768 screen resolution