title: Molecular motions in drug design: the coming age of the metadynamics method.
abstract: Metadynamics is emerging as a useful free energy method in physics, chemistry and biology. Recently, it has been applied also to investigate ligand binding to biomolecules of pharmacological interest. Here, after introducing the basic idea of the method, we review applications to challenging targets for pharmaceutical intervention. We show that this methodology, especially when combined with a variety of other computational approaches such as molecular docking and/or molecular dynamics simulation, may be useful to predict structure and energetics of ligand/target complexes even when the targets lack a deep binding cavity, such as DNA and proteins undergoing fibrillation in neurodegenerative diseases. Furthermore, the method allows investigating the routes of molecular recognition and the associated binding energy profiles, providing a molecular interpretation to experimental data.
authors.affiliation: International School for Advanced Studies, Trieste, Italy.
authors.forename: Xevi
authors.initials: X
authors.lastname: Biarnés
authors.forename: Salvatore
authors.initials: S
authors.lastname: Bongarzone
authors.forename: Attilio Vittorio
authors.initials: AV
authors.lastname: Vargiu
authors.forename: Paolo
authors.initials: P
authors.lastname: Carloni
authors.forename: Paolo
authors.initials: P
authors.lastname: Ruggerone
mesh_terms: D017076:Computer-Aided Design / Q000295:instrumentation; D004247:DNA / Q000737:chemistry* / Q000378:metabolism*; D015195:Drug Design; D008024:Ligands; D056004:Molecular Dynamics Simulation; D009038:Motion; D011485:Protein Binding; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D013816:Thermodynamics
chemical_list: D008024:Ligands; D011506:Proteins; D004247:DNA