Dynamics and calcium association to the N-terminal regulatory domain of human cardiac troponin C: a multiscale computational study.

TitleDynamics and calcium association to the N-terminal regulatory domain of human cardiac troponin C: a multiscale computational study.
Publication TypeJournal Article
Year of Publication2012
JournalThe journal of physical chemistry. B
Volume116
Issue29
Pagination8449-59
Date Published2012
ISSN1520-6106
Abstract

Troponin C (TnC) is an important regulatory molecule in cardiomyocytes. Calcium binding to site II in TnC initiates a series of molecular events that result in muscle contraction. The most direct change upon Ca(2+) binding is an opening motion of the molecule that exposes a hydrophobic patch on the surface allowing for Troponin I to bind. Molecular dynamics simulations were used to elucidate the dynamics of this crucial protein in three different states: apo, Ca(2+)-bound, and Ca(2+)-TnI-bound. Dynamics between the states are compared, and the Ca(2+)-bound system is investigated for opening motions. On the basis of the simulations, NMR chemical shifts and order parameters are calculated and compared with experimental observables. Agreement indicates that the simulations sample the relevant dynamics of the system. Brownian dynamics simulations are used to investigate the calcium association of TnC. We find that calcium binding gives rise to correlative motions involving the EF hand and collective motions conducive of formation of the TnI-binding interface. We furthermore indicate the essential role of electrostatic steering in facilitating diffusion-limited binding of Ca(2+).

URLhttps://dx.doi.org/10.1021/jp212173f
DOI10.1021/jp212173f
Short TitleJ Phys Chem B
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