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Theoretical investigation on the diatomic ligand migration process and ligand binding properties in non‐O 2 ‐binding H‐NOX domain
Author(s) -
Zhang Yuebin,
Liu Li,
Wu Lei,
Li Shuai,
Li Fei,
Li Zhengqiang
Publication year - 2013
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.24279
Subject(s) - ligand (biochemistry) , chemistry , nox , molecular dynamics , diatomic molecule , stereochemistry , crystallography , computational chemistry , molecule , receptor , biochemistry , organic chemistry , combustion
The Nostoc sp ( Ns ) H‐NOX (heme‐nitric oxide or OXygen‐binding) domain shares 35% sequence identity with soluble guanylate cyclase (sGC) and exhibits similar ligand binding property with the sGC. Previously, our molecular dynamic (MD) simulation work identified that there exists a Y‐shaped tunnel system hosted in the Ns H‐NOX interior, which servers for ligand migration. The tunnels were then confirmed by Winter et al . [PNAS 2011;108(43):E 881–889] recently using x‐ray crystallography with xenon pressured conditions. In this work, to further investigate how the protein matrix of Ns H‐NOX modulates the ligand migration process and how the distal residue composition affects the ligand binding prosperities, the free energy profiles for nitric oxide (NO), carbon monooxide (CO), and O 2 migration are explored using the steered MDs simulation and the ligand binding energies are calculated using QM/MM schemes. The potential of mean force profiles suggest that the longer branch of the tunnel would be the most favorable route for NO migration and a second NO trapping site other than the distal heme pocket along this route in the Ns H‐NOX was identified. On the contrary, CO and O 2 would prefer to diffuse via the shorter branch of the tunnel. The QM/MM (quantum mechanics/molecular mechanics) calculations suggest that the hydrophobic distal pocket of Ns H‐NOX would provide an approximately vacuum environment and the ligand discrimination would be determined by the intrinsic binding properties of the diatomic gas ligand to the heme group. Proteins 2013; 81:1363–1376. © 2013 Wiley Periodicals, Inc.