TY - JOUR
T1 - Molecular motions in drug design
T2 - The coming age of the metadynamics method
AU - Biarnés, Xevi
AU - Bongarzone, Salvatore
AU - Vargiu, Attilio Vittorio
AU - Carloni, Paolo
AU - Ruggerone, Paolo
N1 - Funding Information:
Acknowledgments A. V. Vargiu acknowledges financial support from ‘‘Regione Autonoma della Sardegna’’ through a Research Fellow on fundings ‘‘PO Sardegna FSE 2007-2013, L.R.7/2007 Pro-mozione della ricerca scientifica e dell’innovazione tecnologica in Sardegna’’. X. Biarnés acknowledges financial support from ‘‘Gen-eralitat de Catalunya’’ through a ‘‘Beatriu de Pinos’’ research fellow.
PY - 2011/5
Y1 - 2011/5
N2 - 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.
AB - 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.
KW - DNA minor groove
KW - Docking
KW - Metadynamics
KW - Prion Protein
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UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=pure_univeritat_ramon_llull&SrcAuth=WosAPI&KeyUT=WOS:000291261700001&DestLinkType=FullRecord&DestApp=WOS_CPL
U2 - 10.1007/s10822-011-9415-3
DO - 10.1007/s10822-011-9415-3
M3 - Article
C2 - 21327922
AN - SCOPUS:80051674975
SN - 0920-654X
VL - 25
SP - 395
EP - 402
JO - Journal of Computer-Aided Molecular Design
JF - Journal of Computer-Aided Molecular Design
IS - 5
ER -