Effect of Charge Distribution in a Modified tRNA Substrate on Pre-Reaction Protein-tRNA Complex Geometry.
Journal
ACS omega
ISSN: 2470-1343
Titre abrégé: ACS Omega
Pays: United States
ID NLM: 101691658
Informations de publication
Date de publication:
16 Feb 2021
16 Feb 2021
Historique:
received:
22
10
2020
accepted:
21
01
2021
entrez:
1
3
2021
pubmed:
2
3
2021
medline:
2
3
2021
Statut:
epublish
Résumé
An important aspect of molecular mechanics simulations of a protein structure and ligand binding often involves the generation of reliable force fields for nonstandard residues and ligands. We consider the aminoacyl-tRNA synthetase (AaRS) system that involves nucleic acid and amino acid derivatives, obtaining force field atomic charges using the restrained electrostatic potential (RESP) approach. These charges are shown to predict observed properties of the post-transfer editing reaction in this system, in contrast to simulations performed using approximate charges conceived based upon standard charges for related systems present in force field databases. In particular, the simulations predicted key properties induced by mutation. The approach taken for generating the RESP charges retains established charges for known fragments, defining new charges only for the novel chemical features present in the modified residues. This approach is of general relevance for the design of force fields for pharmacological applications, and indeed the AaRS target system is itself relevant to antibiotics development.
Identifiants
pubmed: 33644545
doi: 10.1021/acsomega.0c05143
pmc: PMC7906584
doi:
Types de publication
Journal Article
Langues
eng
Pagination
4227-4235Informations de copyright
© 2021 The Authors. Published by American Chemical Society.
Déclaration de conflit d'intérêts
The authors declare no competing financial interest.
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