First principles calculations of thermodynamics and kinetic parameters and molecular dynamics simulations of acetylcholinesterase reactivators: can mouse data provide new insights into humans?
We have applied a theoretical methodology, previously developed to evaluate the association and kinetic reactivation constants of oximes, comparing theoretical data obtained for human acetylcholinesterase (HsAChE) with in vitro results from Mus musculus AChE (MmAChE) previously reported in the literature. Our results, further checked by additional molecular dynamics simulations steps, showed a good correlation between the theoretical and experimental data, supporting the methodology as appropriate for prediction of thermodynamic and kinetic parameters and corroborated MmAChE as a suitable model for studies with HsAChE.
Department of Chemistry, Federal University of Lavras, Campus Universitário, 37200-000 Lavras, MG, Brazil.
Karina S
KS
Matos
Elaine F F
EF
da Cunha
Arlan
A
da Silva Gonçalves
Alan
A
Wilter
Kamil
K
Kuča
Tanos C C
TC
França
Teodorico C
TC
Ramalho
D000110:Acetylcholinesterase / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000378:metabolism; D002801:Cholinesterase Reactivators / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D051379:Mice; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D010091:Oximes / Q000737:chemistry / Q000378:metabolism*; D016415:Sequence Alignment; D013329:Structure-Activity Relationship; D013816:Thermodynamics
D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D010091:Oximes; D000110:Acetylcholinesterase