Molecular dynamics simulation of class 3 aldehyde dehydrogenase.
Molecular dynamics (MD) simulation of the rat class 3 aldehyde dehydrogenase (ALDH) with nicotinamide dinucleotide (NAD) cofactors and explicit water molecules are reported. Our results demonstrate that MD simulation using the latest methodologies can maintain the crystal structure of the enzyme, as well as closely reproduce the short timescale dynamics of the enzyme. Furthermore, the examination of the distance between the nucleophilic Cys-243 and the NAD cofactor reveal important fluctuations that could be linked to ALDH catalysis. Finally, our quantum mechanical model of benzaldehyde in the active site of ALDH demonstrates that the enzyme requires only minor conformational changes to be poised for nucleophilic attack on the substrate.
Wymore
T
T
Biomedical Initiatives Group, Pittsburgh Supercomputing Center, 4400 Fifth Avenue, 15213, Pittsburgh, PA, USA.
Nicholas
H B
HB
Hempel
J
J
D000444:Aldehyde Dehydrogenase / Q000737:chemistry* / Q000145:classification / Q000378:metabolism; D000818:Animals; D001547:Benzaldehydes / Q000378:metabolism; D020134:Catalytic Domain; D003067:Coenzymes / Q000378:metabolism; D020035:Holoenzymes / Q000737:chemistry / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008956:Models, Chemical; D009243:NAD / Q000378:metabolism; D011789:Quantum Theory; D051381:Rats; D013816:Thermodynamics
D001547:Benzaldehydes; D003067:Coenzymes; D020035:Holoenzymes; C030863:corneal protein 54, bovine; D009243:NAD; D000444:Aldehyde Dehydrogenase; C032175:benzaldehyde