TY - JOUR
T1 - Metadynamics simulations of ligands binding to protein surfaces
T2 - a novel tool for rational drug design
AU - Zuo, Ke
AU - Kranjc, Agata
AU - Capelli, Riccardo
AU - Rossetti, Giulia
AU - Nechushtai, Rachel
AU - Carloni, Paolo
N1 - Publisher Copyright:
© 2023 The Royal Society of Chemistry.
PY - 2023/5/5
Y1 - 2023/5/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85159684686&partnerID=8YFLogxK
U2 - 10.1039/d3cp01388j
DO - 10.1039/d3cp01388j
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C2 - 37184538
AN - SCOPUS:85159684686
SN - 1463-9076
VL - 25
SP - 13819
EP - 13824
JO - Physical Chemistry Chemical Physics
JF - Physical Chemistry Chemical Physics
IS - 20
ER -