Ligand Binding Rate Constants in Heme Proteins Using Markov State Models and Molecular Dynamics Simulations. 2019

Mauro Bringas, and Leandro E Lombardi, and F Javier Luque, and Darío A Estrin, and Luciana Capece
Departamento de Química Inorgánica, Analítica y Química Física, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, C1428EGA, Buenos Aires, Argentina.

Computer simulation studies of the molecular basis for ligand migration in proteins allow the description of key events such as the transition between docking sites, displacement of existing ligands and solvent molecules, and open/closure of specific "gates", among others. In heme proteins, ligand migration from the solvent to the active site preludes the binding to the heme iron and triggers different functions. In this work, molecular dynamics simulations, a Markov State Model of migration and empirical kinetic equations are combined to study the migration of O2 and NO in two truncated hemoglobins of Mycobacterium tuberculosis (Mt-TrHbN and Mt-TrHbO). For Mt-TrHbN, we show that the difference in the association constant in the oxy and deoxy states relies mainly in the displacement of water molecules anchored in the distal cavity in the deoxy form. The results here provide a valuable approach to study ligand migration in globins.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008024 Ligands A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed) Ligand
D008390 Markov Chains A stochastic process such that the conditional probability distribution for a state at any future instant, given the present state, is unaffected by any additional knowledge of the past history of the system. Markov Process,Markov Chain,Chain, Markov,Chains, Markov,Markov Processes,Process, Markov,Processes, Markov
D009169 Mycobacterium tuberculosis A species of gram-positive, aerobic bacteria that produces TUBERCULOSIS in humans, other primates, CATTLE; DOGS; and some other animals which have contact with humans. Growth tends to be in serpentine, cordlike masses in which the bacilli show a parallel orientation. Mycobacterium tuberculosis H37Rv
D009569 Nitric Oxide A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP. Endogenous Nitrate Vasodilator,Mononitrogen Monoxide,Nitric Oxide, Endothelium-Derived,Nitrogen Monoxide,Endothelium-Derived Nitric Oxide,Monoxide, Mononitrogen,Monoxide, Nitrogen,Nitrate Vasodilator, Endogenous,Nitric Oxide, Endothelium Derived,Oxide, Nitric,Vasodilator, Endogenous Nitrate
D010100 Oxygen An element with atomic symbol O, atomic number 8, and atomic weight [15.99903; 15.99977]. It is the most abundant element on earth and essential for respiration. Dioxygen,Oxygen-16,Oxygen 16
D006454 Hemoglobins The oxygen-carrying proteins of ERYTHROCYTES. They are found in all vertebrates and some invertebrates. The number of globin subunits in the hemoglobin quaternary structure differs between species. Structures range from monomeric to a variety of multimeric arrangements. Eryhem,Ferrous Hemoglobin,Hemoglobin,Hemoglobin, Ferrous
D001665 Binding Sites The parts of a macromolecule that directly participate in its specific combination with another molecule. Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining
D056004 Molecular Dynamics Simulation A computer simulation developed to study the motion of molecules over a period of time. Molecular Dynamics Simulations,Molecular Dynamics,Dynamic, Molecular,Dynamics Simulation, Molecular,Dynamics Simulations, Molecular,Dynamics, Molecular,Molecular Dynamic,Simulation, Molecular Dynamics,Simulations, Molecular Dynamics

Related Publications

Mauro Bringas, and Leandro E Lombardi, and F Javier Luque, and Darío A Estrin, and Luciana Capece
September 2008, Journal of theoretical biology,
Mauro Bringas, and Leandro E Lombardi, and F Javier Luque, and Darío A Estrin, and Luciana Capece
January 2020, Progress in molecular biology and translational science,
Mauro Bringas, and Leandro E Lombardi, and F Javier Luque, and Darío A Estrin, and Luciana Capece
September 2019, Journal of chemical theory and computation,
Mauro Bringas, and Leandro E Lombardi, and F Javier Luque, and Darío A Estrin, and Luciana Capece
November 2020, Journal of chemical information and modeling,
Mauro Bringas, and Leandro E Lombardi, and F Javier Luque, and Darío A Estrin, and Luciana Capece
May 2018, Journal of chemical theory and computation,
Mauro Bringas, and Leandro E Lombardi, and F Javier Luque, and Darío A Estrin, and Luciana Capece
March 2019, The Journal of chemical physics,
Mauro Bringas, and Leandro E Lombardi, and F Javier Luque, and Darío A Estrin, and Luciana Capece
January 2021, Methods in molecular biology (Clifton, N.J.),
Mauro Bringas, and Leandro E Lombardi, and F Javier Luque, and Darío A Estrin, and Luciana Capece
August 1979, Journal of molecular biology,
Mauro Bringas, and Leandro E Lombardi, and F Javier Luque, and Darío A Estrin, and Luciana Capece
June 2002, Proceedings of the National Academy of Sciences of the United States of America,
Mauro Bringas, and Leandro E Lombardi, and F Javier Luque, and Darío A Estrin, and Luciana Capece
November 2008, Biophysical chemistry,
Copied contents to your clipboard!