Solvents to fragments to drugs: MD applications in drug design

Simulations of molecular dynamics (MD) are playing an increasingly important role in structure-based drug discovery (SBDD). Here we review the use of MD for proteins in aqueous solvation, organic/aqueous mixed solvents (MDmix) and with small ligands, to the classic SBDD problems: Binding mode and bi...

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Autores principales:	Defelipe, L.A., Arcon, J.P., Modenutti, C.P., Marti, M.A., Turjanski, A.G., Barril, X.
Formato:	JOUR
Materias:	Cosolvent molecular dynamics Docking Drug design Fragment screening Molecular dynamics ligand protein solvent chemistry drug design drug development metabolism molecular dynamics Drug Design Drug Discovery Ligands Molecular Dynamics Simulation Proteins Solvents
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_14203049_v23_n12_p_Defelipe
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	todo:paper_14203049_v23_n12_p_Defelipe
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spelling	todo:paper_14203049_v23_n12_p_Defelipe2023-10-03T16:13:14Z Solvents to fragments to drugs: MD applications in drug design Defelipe, L.A. Arcon, J.P. Modenutti, C.P. Marti, M.A. Turjanski, A.G. Barril, X. Cosolvent molecular dynamics Docking Drug design Fragment screening Molecular dynamics ligand protein solvent chemistry drug design drug development metabolism molecular dynamics Drug Design Drug Discovery Ligands Molecular Dynamics Simulation Proteins Solvents Simulations of molecular dynamics (MD) are playing an increasingly important role in structure-based drug discovery (SBDD). Here we review the use of MD for proteins in aqueous solvation, organic/aqueous mixed solvents (MDmix) and with small ligands, to the classic SBDD problems: Binding mode and binding free energy predictions. The simulation of proteins in their condensed state reveals solvent structures and preferential interaction sites (hot spots) on the protein surface. The information provided by water and its cosolvents can be used very effectively to understand protein ligand recognition and to improve the predictive capability of well-established methods such as molecular docking. The application of MD simulations to the study of the association of proteins with drug-like compounds is currently only possible for specific cases, as it remains computationally very expensive and labor intensive. MDmix simulations on the other hand, can be used systematically to address some of the common tasks in SBDD. With the advent of new tools and faster computers we expect to see an increase in the application of mixed solvent MD simulations to a plethora of protein targets to identify new drug candidates. © 2018 by the authors. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_14203049_v23_n12_p_Defelipe
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	Cosolvent molecular dynamics Docking Drug design Fragment screening Molecular dynamics ligand protein solvent chemistry drug design drug development metabolism molecular dynamics Drug Design Drug Discovery Ligands Molecular Dynamics Simulation Proteins Solvents
spellingShingle	Cosolvent molecular dynamics Docking Drug design Fragment screening Molecular dynamics ligand protein solvent chemistry drug design drug development metabolism molecular dynamics Drug Design Drug Discovery Ligands Molecular Dynamics Simulation Proteins Solvents Defelipe, L.A. Arcon, J.P. Modenutti, C.P. Marti, M.A. Turjanski, A.G. Barril, X. Solvents to fragments to drugs: MD applications in drug design
topic_facet	Cosolvent molecular dynamics Docking Drug design Fragment screening Molecular dynamics ligand protein solvent chemistry drug design drug development metabolism molecular dynamics Drug Design Drug Discovery Ligands Molecular Dynamics Simulation Proteins Solvents
description	Simulations of molecular dynamics (MD) are playing an increasingly important role in structure-based drug discovery (SBDD). Here we review the use of MD for proteins in aqueous solvation, organic/aqueous mixed solvents (MDmix) and with small ligands, to the classic SBDD problems: Binding mode and binding free energy predictions. The simulation of proteins in their condensed state reveals solvent structures and preferential interaction sites (hot spots) on the protein surface. The information provided by water and its cosolvents can be used very effectively to understand protein ligand recognition and to improve the predictive capability of well-established methods such as molecular docking. The application of MD simulations to the study of the association of proteins with drug-like compounds is currently only possible for specific cases, as it remains computationally very expensive and labor intensive. MDmix simulations on the other hand, can be used systematically to address some of the common tasks in SBDD. With the advent of new tools and faster computers we expect to see an increase in the application of mixed solvent MD simulations to a plethora of protein targets to identify new drug candidates. © 2018 by the authors.
format	JOUR
author	Defelipe, L.A. Arcon, J.P. Modenutti, C.P. Marti, M.A. Turjanski, A.G. Barril, X.
author_facet	Defelipe, L.A. Arcon, J.P. Modenutti, C.P. Marti, M.A. Turjanski, A.G. Barril, X.
author_sort	Defelipe, L.A.
title	Solvents to fragments to drugs: MD applications in drug design
title_short	Solvents to fragments to drugs: MD applications in drug design
title_full	Solvents to fragments to drugs: MD applications in drug design
title_fullStr	Solvents to fragments to drugs: MD applications in drug design
title_full_unstemmed	Solvents to fragments to drugs: MD applications in drug design
title_sort	solvents to fragments to drugs: md applications in drug design
url	http://hdl.handle.net/20.500.12110/paper_14203049_v23_n12_p_Defelipe
work_keys_str_mv	AT defelipela solventstofragmentstodrugsmdapplicationsindrugdesign AT arconjp solventstofragmentstodrugsmdapplicationsindrugdesign AT modenutticp solventstofragmentstodrugsmdapplicationsindrugdesign AT martima solventstofragmentstodrugsmdapplicationsindrugdesign AT turjanskiag solventstofragmentstodrugsmdapplicationsindrugdesign AT barrilx solventstofragmentstodrugsmdapplicationsindrugdesign
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Solvents to fragments to drugs: MD applications in drug design

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