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Ligand Binding Rate Constants in Heme Proteins Using Markov State Models and Molecular Dynamics Simulations
Author(s) -
Bringas Mauro,
Lombardi Leandro E.,
Luque F. Javier,
Estrin Darío A.,
Capece Luciana
Publication year - 2019
Publication title -
chemphyschem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.016
H-Index - 140
eISSN - 1439-7641
pISSN - 1439-4235
DOI - 10.1002/cphc.201900589
Subject(s) - molecular dynamics , chemistry , heme , ligand (biochemistry) , molecule , globin , computational chemistry , stereochemistry , hemoglobin , biochemistry , enzyme , receptor , organic chemistry
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 O 2 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.