Issue 20, 2023

Metadynamics simulations of ligands binding to protein surfaces: a novel tool for rational drug design

Abstract

Structure-based drug design protocols may encounter difficulties to investigate poses when the biomolecular targets do not exhibit typical binding pockets. In this study, by providing two concrete examples from our labs, we suggest that the combination of metadynamics free energy methods (validated against affinity measurements), along with experimental structural information (by X-ray crystallography and NMR), can help to identify the poses of ligands on protein surfaces. The simulation workflow proposed here was implemented in a widely used code, namely GROMACS, and it could straightforwardly be applied to various drug-design campaigns targeting ligands’ binding to protein surfaces.

Graphical abstract: Metadynamics simulations of ligands binding to protein surfaces: a novel tool for rational drug design

Supplementary files

Article information

Article type
Perspective
Submitted
27 mar 2023
Accepted
01 may 2023
First published
05 may 2023
This article is Open Access
Creative Commons BY license

Phys. Chem. Chem. Phys., 2023,25, 13819-13824

Metadynamics simulations of ligands binding to protein surfaces: a novel tool for rational drug design

K. Zuo, A. Kranjc, R. Capelli, G. Rossetti, R. Nechushtai and P. Carloni, Phys. Chem. Chem. Phys., 2023, 25, 13819 DOI: 10.1039/D3CP01388J

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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