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.
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, P. Carloni. - In: PHYSICAL CHEMISTRY CHEMICAL PHYSICS. - ISSN 1463-9076. - 25:20(2023 May 24), pp. 13819-13824. [10.1039/d3cp01388j]
Metadynamics simulations of ligands binding to protein surfaces: a novel tool for rational drug design
R. Capelli;
2023
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.File | Dimensione | Formato | |
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