Premium
On the Quest of Dioxygen by Monomeric Sarcosine Oxidase. A Molecular Dynamics Investigation
Author(s) -
Pietra Francesco
Publication year - 2015
Publication title -
chemistry and biodiversity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.427
H-Index - 70
eISSN - 1612-1880
pISSN - 1612-1872
DOI - 10.1002/cbdv.201400362
Subject(s) - chemistry , sarcosine , molecular dynamics , cofactor , flavoprotein , flavin group , monomer , stereochemistry , flavin adenine dinucleotide , solvent , oxidase test , chemical physics , biophysics , computational chemistry , amino acid , enzyme , biochemistry , organic chemistry , glycine , polymer , biology
Abstract It is reported here on random acceleration molecular dynamics (RAMD) simulations with the 2GF3 bacterial monomeric sarcosine oxidase (MSOX), O 2 , and furoic acid in place of sarcosine, solvated by TIP3 H 2 O in a periodic box. An external tiny force, acting randomly on O 2 , accelerated its relocation, from the center of activation between residue K265 and the si face of the flavin ring of the flavin adenine dinucleotide cofactor, to the surrounding solvent. Only three of the four O 2 gates previously described for this system along a composite method technique were identified, while two more major O 2 gates were found. The RAMD simulations also revealed that the same gate can be reached by O 2 along different pathways, often involving traps for O 2 . Both the residence time of O 2 in the traps, and the total trajectory time for O 2 getting to the solvent, could be evaluated. The new quick pathways discovered here suggest that O 2 exploits all nearby interstices created by the thermal fluctuations of the protein, not having necessarily to look for the permanent large channel used for uptake of the FADH cofactor. To this regard, MSOX resembles closely KijD3 N ‐oxygenase. These observations solicit experimental substantiation, in a long term aim at discovering whether gates and pathways for the small gaseous ligands inside the proteins are under Darwinian functional evolution or merely stochastic control operates.