Probing the Suitability of Different Ca2+ Parameters for Long Simulations of Diisopropyl Fluorophosphatase.
Molecules
; 26(19)2021 Sep 26.
Article
em En
| MEDLINE
| ID: mdl-34641383
ABSTRACT
Organophosphate hydrolases are promising as potential biotherapeutic agents to treat poisoning with pesticides or nerve gases. However, these enzymes often need to be further engineered in order to become useful in practice. One example of such enhancement is the alteration of enantioselectivity of diisopropyl fluorophosphatase (DFPase). Molecular modeling techniques offer a unique opportunity to address this task rationally by providing a physical description of the substrate-binding process. However, DFPase is a metalloenzyme, and correct modeling of metal cations is a challenging task generally coming with a tradeoff between simulation speed and accuracy. Here, we probe several molecular mechanical parameter combinations for their ability to empower long simulations needed to achieve a quantitative description of substrate binding. We demonstrate that a combination of the Amber19sb force field with the recently developed 12-6 Ca2+ models allows us to both correctly model DFPase and obtain new insights into the DFP binding process.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Cálcio
/
Hidrolases de Triester Fosfórico
/
Simulação de Dinâmica Molecular
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article