Comparing and combining implicit ligand sampling with multiple steered molecular dynamics to study ligand migration processes in heme proteins

The ubiquitous heme proteins perform a wide variety of tasks that rely on the subtle regulation of their affinity for small ligands like O2, CO, and NO. Ligand affinity is characterized by kinetic association and dissociation rate constants, that partially depend on ligand migration between the solv...

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Autores principales:	Boechi, Leonardo, Estrin, Dario Ariel, Martí, Marcelo Adrián
Publicado:	2011
Materias:	AMBER cavities CO docking sites free energy profile ILS implicit ligand sampling ligand migration MD molecular dynamics MSMD multiple steered molecular dynamics nitrophorin NO O2 proteins truncated haemoglobin tunnels xenon sites Haemoglobins Nitrophorin Steered molecular dynamics Dissociation Dynamics Free energy Ligands Molecular dynamics Porphyrins Rate constants Proteins carbon monoxide hemoprotein ligand nitric oxide oxygen chemistry kinetics thermodynamics Carbon Monoxide Hemeproteins Kinetics Molecular Dynamics Simulation Nitric Oxide Oxygen Thermodynamics
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01928651_v32_n10_p2219_Forti http://hdl.handle.net/20.500.12110/paper_01928651_v32_n10_p2219_Forti
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paper:paper_01928651_v32_n10_p2219_Forti
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spelling	paper:paper_01928651_v32_n10_p2219_Forti2023-06-08T15:20:00Z Comparing and combining implicit ligand sampling with multiple steered molecular dynamics to study ligand migration processes in heme proteins Boechi, Leonardo Estrin, Dario Ariel Martí, Marcelo Adrián AMBER cavities CO docking sites free energy profile ILS implicit ligand sampling ligand migration MD molecular dynamics MSMD multiple steered molecular dynamics nitrophorin NO O2 proteins truncated haemoglobin tunnels xenon sites cavities docking sites free energy profile Haemoglobins ILS implicit ligand sampling MSMD Nitrophorin Steered molecular dynamics Dissociation Dynamics Free energy Ligands Molecular dynamics Porphyrins Rate constants Proteins carbon monoxide hemoprotein ligand nitric oxide oxygen chemistry kinetics molecular dynamics thermodynamics Carbon Monoxide Hemeproteins Kinetics Ligands Molecular Dynamics Simulation Nitric Oxide Oxygen Thermodynamics The ubiquitous heme proteins perform a wide variety of tasks that rely on the subtle regulation of their affinity for small ligands like O2, CO, and NO. Ligand affinity is characterized by kinetic association and dissociation rate constants, that partially depend on ligand migration between the solvent and active site, mediated by the presence of internal cavities or tunnels. Different computational methods have been developed to study these processes which can be roughly divided in two strategies: those costly methods in which the ligand is treated explicitly during the simulations, and the free energy landscape of the process is computed; and those faster methods that use prior computed Molecular Dynamics simulation without the ligand, and incorporate it afterwards, called implicit ligand sampling (ILS) methods. To compare both approaches performance and to provide a combined protocol to study ligand migration in heme proteins, we performed ILS and multiple steered molecular dynamics (MSMD) free energy calculations of the ligand migration process in three representative and well theoretically and experimentally studied cases that cover a wide range of complex situations presenting a challenging benchmark for the aim of the present work. Our results show that ILS provides a good description of the tunnel topology and a reasonable approximation to the free energy landscape, while MSMD provides more accurate and detailed free energy profile description of each tunnel. Based on these results, a combined strategy is presented for the study of internal ligand migration in heme proteins. © 2011 Wiley Periodicals, Inc. Fil:Boechi, L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Estrin, D.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Marti, M.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2011 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01928651_v32_n10_p2219_Forti http://hdl.handle.net/20.500.12110/paper_01928651_v32_n10_p2219_Forti
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	AMBER cavities CO docking sites free energy profile ILS implicit ligand sampling ligand migration MD molecular dynamics MSMD multiple steered molecular dynamics nitrophorin NO O2 proteins truncated haemoglobin tunnels xenon sites cavities docking sites free energy profile Haemoglobins ILS implicit ligand sampling MSMD Nitrophorin Steered molecular dynamics Dissociation Dynamics Free energy Ligands Molecular dynamics Porphyrins Rate constants Proteins carbon monoxide hemoprotein ligand nitric oxide oxygen chemistry kinetics molecular dynamics thermodynamics Carbon Monoxide Hemeproteins Kinetics Ligands Molecular Dynamics Simulation Nitric Oxide Oxygen Thermodynamics
spellingShingle	AMBER cavities CO docking sites free energy profile ILS implicit ligand sampling ligand migration MD molecular dynamics MSMD multiple steered molecular dynamics nitrophorin NO O2 proteins truncated haemoglobin tunnels xenon sites cavities docking sites free energy profile Haemoglobins ILS implicit ligand sampling MSMD Nitrophorin Steered molecular dynamics Dissociation Dynamics Free energy Ligands Molecular dynamics Porphyrins Rate constants Proteins carbon monoxide hemoprotein ligand nitric oxide oxygen chemistry kinetics molecular dynamics thermodynamics Carbon Monoxide Hemeproteins Kinetics Ligands Molecular Dynamics Simulation Nitric Oxide Oxygen Thermodynamics Boechi, Leonardo Estrin, Dario Ariel Martí, Marcelo Adrián Comparing and combining implicit ligand sampling with multiple steered molecular dynamics to study ligand migration processes in heme proteins
topic_facet	AMBER cavities CO docking sites free energy profile ILS implicit ligand sampling ligand migration MD molecular dynamics MSMD multiple steered molecular dynamics nitrophorin NO O2 proteins truncated haemoglobin tunnels xenon sites cavities docking sites free energy profile Haemoglobins ILS implicit ligand sampling MSMD Nitrophorin Steered molecular dynamics Dissociation Dynamics Free energy Ligands Molecular dynamics Porphyrins Rate constants Proteins carbon monoxide hemoprotein ligand nitric oxide oxygen chemistry kinetics molecular dynamics thermodynamics Carbon Monoxide Hemeproteins Kinetics Ligands Molecular Dynamics Simulation Nitric Oxide Oxygen Thermodynamics
description	The ubiquitous heme proteins perform a wide variety of tasks that rely on the subtle regulation of their affinity for small ligands like O2, CO, and NO. Ligand affinity is characterized by kinetic association and dissociation rate constants, that partially depend on ligand migration between the solvent and active site, mediated by the presence of internal cavities or tunnels. Different computational methods have been developed to study these processes which can be roughly divided in two strategies: those costly methods in which the ligand is treated explicitly during the simulations, and the free energy landscape of the process is computed; and those faster methods that use prior computed Molecular Dynamics simulation without the ligand, and incorporate it afterwards, called implicit ligand sampling (ILS) methods. To compare both approaches performance and to provide a combined protocol to study ligand migration in heme proteins, we performed ILS and multiple steered molecular dynamics (MSMD) free energy calculations of the ligand migration process in three representative and well theoretically and experimentally studied cases that cover a wide range of complex situations presenting a challenging benchmark for the aim of the present work. Our results show that ILS provides a good description of the tunnel topology and a reasonable approximation to the free energy landscape, while MSMD provides more accurate and detailed free energy profile description of each tunnel. Based on these results, a combined strategy is presented for the study of internal ligand migration in heme proteins. © 2011 Wiley Periodicals, Inc.
author	Boechi, Leonardo Estrin, Dario Ariel Martí, Marcelo Adrián
author_facet	Boechi, Leonardo Estrin, Dario Ariel Martí, Marcelo Adrián
author_sort	Boechi, Leonardo
title	Comparing and combining implicit ligand sampling with multiple steered molecular dynamics to study ligand migration processes in heme proteins
title_short	Comparing and combining implicit ligand sampling with multiple steered molecular dynamics to study ligand migration processes in heme proteins
title_full	Comparing and combining implicit ligand sampling with multiple steered molecular dynamics to study ligand migration processes in heme proteins
title_fullStr	Comparing and combining implicit ligand sampling with multiple steered molecular dynamics to study ligand migration processes in heme proteins
title_full_unstemmed	Comparing and combining implicit ligand sampling with multiple steered molecular dynamics to study ligand migration processes in heme proteins
title_sort	comparing and combining implicit ligand sampling with multiple steered molecular dynamics to study ligand migration processes in heme proteins
publishDate	2011
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01928651_v32_n10_p2219_Forti http://hdl.handle.net/20.500.12110/paper_01928651_v32_n10_p2219_Forti
work_keys_str_mv	AT boechileonardo comparingandcombiningimplicitligandsamplingwithmultiplesteeredmoleculardynamicstostudyligandmigrationprocessesinhemeproteins AT estrindarioariel comparingandcombiningimplicitligandsamplingwithmultiplesteeredmoleculardynamicstostudyligandmigrationprocessesinhemeproteins AT martimarceloadrian comparingandcombiningimplicitligandsamplingwithmultiplesteeredmoleculardynamicstostudyligandmigrationprocessesinhemeproteins
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Comparing and combining implicit ligand sampling with multiple steered molecular dynamics to study ligand migration processes in heme proteins

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