Atomic-resolution dissection of the energetics and mechanism of isomerization of hydrated ATP-Mg(2+) through the SOMA string method.
J Comput Chem
; 37(6): 575-86, 2016 Mar 05.
Article
em En
| MEDLINE
| ID: mdl-26149527
ABSTRACT
The atomic mechanisms of isomerization of ATP-Mg(2+) in solution are characterized using the recently developed String Method with Optimal Molecular Alignment (SOMA) and molecular-dynamics simulations. Bias-Exchange Metadynamics simulations are first performed to identify the primary conformers of the ATP-Mg(2+) complex and their connectivity. SOMA is then used to elucidate the minimum free-energy path (MFEP) for each transition, in a 48-dimensional space. Analysis of the per-atom contributions to the global free-energy profiles reveals that the mechanism of these transitions is controlled by the Mg(2+) ion and its coordinating oxygen atoms in the triphosphate moiety, as well as by the ion-hydration shell. Metadynamics simulations in path collective variables based on the MFEP demonstrate these isomerizations proceed across a narrow channel of configurational space, thus validating the premise underlying SOMA. This study provides a roadmap for the examination of conformational changes in biomolecules, based on complementary enhanced-sampling techniques with different strengths. © 2015 Wiley Periodicals, Inc.
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1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Água
/
Trifosfato de Adenosina
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
J Comput Chem
Assunto da revista:
QUIMICA
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Alemanha