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The effects of the L29F mutation on the ligand migration kinetics in crystallized myoglobin as revealed by molecular dynamics simulations
Author(s) -
Anselmi Massimiliano,
Di Nola Alfredo,
Amadei Andrea
Publication year - 2011
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.22924
Subject(s) - myoglobin , kinetics , chemistry , molecular dynamics , ligand (biochemistry) , carbon monoxide , diffusion , relaxation (psychology) , protein dynamics , mutant , biophysics , crystallography , computational chemistry , thermodynamics , biochemistry , biology , gene , physics , receptor , quantum mechanics , neuroscience , catalysis
By using multiple molecular dynamics (MD) trajectories, a quantitative description of carbon monoxide (CO) migration within crystal of L29F myoglobin mutant (L29F‐Mb) was obtained. The aim was to provide a detailed model for ligand diffusion in the protein to be compared to the available L29F‐Mb experimental‐computational data and to the corresponding model kinetics we previously obtained for photolyzed CO within crystallized wild‐type myoglobin (wt‐Mb). Results suggest a clear migration pathway from distal pocket to the proximal site, similar to the one observed in wt‐Mb, with a relaxation kinetics differing from the wt‐Mb one essentially for the escape rate which is much higher in the mutant. Moreover MD data indicated a clear correlation between CO location within the protein and the conformation adopted by Phe29, well matching the available experimental data as obtained by time‐resolved X‐ray density maps. Such data, further validating the model used in the simulations, point out the subtle mutual effect between ligand diffusion and protein functional motions possibly explaining the observed dramatic variation of CO exit rate in L29F‐Mb. Proteins 2011. © 2010 Wiley‐Liss, Inc.