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Atomic‐resolution dissection of the energetics and mechanism of isomerization of hydrated ATP ‐ M g 2+ through the SOMA string method
Author(s) -
Branduardi Davide,
Marinelli Fabrizio,
FaraldoGómez José D.
Publication year - 2016
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/jcc.23991
Subject(s) - metadynamics , isomerization , chemistry , soma , chemical physics , ion , energy landscape , conformational isomerism , molecular dynamics , computational chemistry , molecule , biochemistry , organic chemistry , neuroscience , biology , catalysis
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.