Novel Lennard-Jones Parameters for Cysteine and Selenocysteine in the AMBER Force Field

Cysteine is a common amino acid with a thiol group that plays a pivotal role in a variety of scenarios in redox biochemistry. In contrast, selenocysteine, the 21st amino acid, is only present in 25 human proteins. Classical force-field parameters for cysteine and selenocysteine are still scarce. In...

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Bibliographic Details
Published in:Journal of chemical information and modeling 2023-01, Vol.63 (2), p.595-604
Main Authors: Pedron, Federico N., Messias, Andresa, Zeida, Ari, Roitberg, Adrián E., Estrin, Darío A.
Format: Article
Language:English
Subjects:
Amino acids
Amino Acids - chemistry
Computational Biochemistry
Cysteine
Density functional theory
Distribution functions
Dynamic structural analysis
Functionals
Humans
Molecular dynamics
Molecular Dynamics Simulation
Molecular structure
Oxidation
Parameters
Proteins
Proteins - chemistry
Protonation
Radial distribution
Residues
Selenocysteine
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Summary:Cysteine is a common amino acid with a thiol group that plays a pivotal role in a variety of scenarios in redox biochemistry. In contrast, selenocysteine, the 21st amino acid, is only present in 25 human proteins. Classical force-field parameters for cysteine and selenocysteine are still scarce. In this context, we present a methodology to obtain Lennard-Jones parameters for cysteine and selenocysteine in different physiologically relevant oxidation and protonation states. The new force field parameters obtained in this work are available at https://github.com/MALBECC/AMBER-parameters-database. The parameters were adjusted to reproduce water radial distribution functions obtained by density functional theory ab initio molecular dynamics. We validated the results by evaluating the impact of the choice of parameters on the structure and dynamics in classical molecular dynamics simulations of representative proteins containing catalytic cysteine/selenocysteine residues. There are significant changes in protein structure and dynamics depending on the parameters choice, specifically affecting the residues close to the catalytic sites.
ISSN:1549-9596
1549-960X
DOI:10.1021/acs.jcim.2c01104