Page 62 - GPD-3-1

Gene & Protein in Disease

SHORT COMMUNICATION
On the in silico application of the center-of-mass

distance method

Done Stojanov*
Department of Computer Technologies and Intelligent Systems, Faculty of Computer Science, Goce
Delcev University, Stip, North Macedonia

Abstract
This study aims to protocolize the utilization of the center-of-mass (CoM) distance
method in GROMACS MD simulation software as a useful method for evaluating
the binding affinity change in heterodimeric protein due to induced changes in
one of the units. The hypothesis underlines the basic principles in biophysics, that
an increase of the binding affinity is expected to reduce the relative CoM distance
between monomers, while the opposite is expected to increase the relative CoM
distance. However, it has been found that the CoM distance analysis must be
strictly preformed during the convergent phase of systems’ dynamics, once the
monomers enter mutually stable conformation — a limitation which has usually
been overlooked. The method was used to study the impact of K417Y severe acute
respiratory syndrome coronavirus 2 (SARS-CoV-2) surface glycoprotein (S-protein)
mutation. It has been found that the K417Y mutation favors reduced binding affinity
between SARS-CoV-2 S-protein and human angiotensin-converting enzyme 2
(hACE2) receptor, which is due to the loss of the permanent K417-D30 salt bridge in
favor of a temporary Y417-D30 hydrogen bond. The destabilizing impact of K417Y
mutation on S-protein–hACE2 complex was confirmed by radius of gyration analysis.

*Corresponding author:
Done Stojanov Keywords: GROMACS; Simulation; Center-of-mass; Distance; K417Y mutation; SARS-CoV-2
(done.stojanov@ugd.edu.mk)
Citation: Stojanov D. On the in
silico application of the center-
of-mass distance method. Gene 1. Introduction
Protein Dis. 2024;3(1):2657.
https://doi.org/10.36922/gpd.2657 The center-of-mass (CoM) distance method can be formally defined as a time continuous
Received: January 6, 2024 analysis of the distance between the CoM of two structures, which constitute together a
1
Accepted: February 29, 2024 common system of interest, such as monomers in heterodimer, protein-ligand complex,
2
Published Online: March 15, 2024 or a pair of key residues. 3
Copyright: © 2024 Author(s).
This is an Open-Access article The core definition of the CoM distance method has been applied in several in silico
2-5
2
distributed under the terms of the studies. Ibrahim et al., compared inhibitor activity of erylosides B and lopinavir
Creative Commons Attribution against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease,
License, permitting distribution,
and reproduction in any medium, using molecular dynamics (MD) simulations in addition to generalized born surface
provided the original work is area binding energy calculations. MM/GBSA (molecular mechanics with generalized
properly cited. Born and surface area solvation) is used as a method to snapshot the free energy of
Publisher’s Note: AccScience the biding between ligands (erylosides B and lopinavir, specifically) to the SARS-CoV-2
Publishing remains neutral with main protease, which involves MD simulations with an explicit water solvent of the
regard to jurisdictional claims in 6
published maps and institutional protein-ligand complex. One of the methods used to show that erylosides B exhibits
affiliations. higher inhibitor activity against SARS-CoV-2 main protease than lopinavir is the CoM

Volume 3 Issue 1 (2024) 1 https://doi.org/10.36922/gpd.2657