A Molecular Mechanics Model for Flavins.
CHAMM
flavin
flavin adenine nucleotide
flavin mononucleotide
flavoprotein
force field
molecular dynamics
riboflavin
Journal
Journal of computational chemistry
ISSN: 1096-987X
Titre abrégé: J Comput Chem
Pays: United States
ID NLM: 9878362
Informations de publication
Date de publication:
15 12 2019
15 12 2019
Historique:
received:
11
04
2019
revised:
03
07
2019
accepted:
04
08
2019
pubmed:
1
9
2019
medline:
12
8
2020
entrez:
1
9
2019
Statut:
ppublish
Résumé
Flavin containing molecules form a group of important cofactors that assist a wide range of enzymatic reactions. Flavins use the redox-active isoalloxazine system, which is capable of one- and two-electron transfer reactions and can exist in several protonation states. In this work, molecular mechanics force field parameters compatible with the CHARMM36 all-atom additive force field were derived for biologically important flavins, including riboflavin, flavin mononucleotide, and flavin adenine dinucleotide. The model was developed for important protonation and redox states of the isoalloxazine group. The partial charges were derived using the CHARMM force field parametrization strategy, where quantum mechanics water-solute interactions are used to target optimization. In addition to monohydrate energies and geometries, electrostatic potential around the compound was used to provide additional restraints during the charge optimization. Taking into account the importance of flavin-containing molecules special attention was given to the quality of bonded terms. All bonded terms, including stiff terms and torsion angle parameters, were parametrized using exhaustive potential energy surface scans. In particular, the model reproduces well the butterfly motion of isoalloxazine in the oxidized and reduced forms as predicted by quantum mechanics in gas phase. The model quality is illustrated by simulations of four flavoproteins. Overall, the presented molecular mechanics model will be of utility to model flavin cofactors in different redox states. © 2019 Wiley Periodicals, Inc.
Substances chimiques
Flavins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2834-2842Informations de copyright
© 2019 Wiley Periodicals, Inc.
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