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Troponin (Tn) is an important regulatory protein in the thin-filament complex of cardiomyocytes. Calcium binding to the troponin C (TnC) subunit causes a change in its dynamics that leads to the transient opening of a hydrophobic patch on TnC's surface, to which a helix of another subunit, troponin I (TnI), binds. This process initiates contraction, making(More)
To help improve the accuracy of protein-ligand docking as a useful tool for drug discovery, we developed MPSim-Dock, which ensures a comprehensive sampling of diverse families of ligand conformations in the binding region followed by an enrichment of the good energy scoring families so that the energy scores of the sampled conformations can be reliably used(More)
Triggered release of Ca2+ from an individual sarcoplasmic reticulum (SR) Ca(2+) release unit (CRU) is the fundamental event of cardiac excitation–contraction coupling, and spontaneous release events (sparks) are the major contributor to diastolic Ca(2+) leak in cardiomyocytes. Previous model studies have predicted that the duration and magnitude of the(More)
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(More)
Troponin C (TnC) is implicated in the initiation of myocyte contraction via binding of cytosolic Ca²⁺ and subsequent recognition of the Troponin I switch peptide. Mutations of the cardiac TnC N-terminal regulatory domain have been shown to alter both calcium binding and myofilament force generation. We have performed molecular dynamics simulations of(More)
The transverse tubular system of rabbit ventricular myocytes consists of cell membrane invaginations (t-tubules) that are essential for efficient cardiac excitation-contraction coupling. In this study, we investigate how t-tubule micro-anatomy, L-type Ca(2+) channel (LCC) clustering, and allosteric activation of Na(+)/Ca(2+) exchanger by L-type Ca(2+)(More)
Aminoacyl-tRNA synthetases guard the fidelity of cognate amino acid incorporation during protein biosynthesis; for example, phenylalanyl-tRNA synthetase (PheRS) activates and transfers only Phe to its tRNA. Since we are interested in using a computational protocol to identify nonnatural amino acids that are incorporated by wild-type PheRS, it is critical to(More)
Contractile function of cardiac cells is driven by the sliding displacement of myofilaments powered by the cycling myosin crossbridges. Critical to this process is the availability of ATP, which myosin hydrolyzes during the cross-bridge cycle. The diffusion of adenine nucleotides through the myofilament lattice has been shown to be anisotropic, with slower(More)
Control of calcium binding to and dissociation from cardiac troponin C (TnC) is essential to healthy cardiac muscle contraction/relaxation. There are numerous aberrant post-translational modifications and mutations within a plethora of contractile, and even non-contractile, proteins that appear to imbalance this delicate relationship. The direction and(More)
The micro-architecture of the transverse tubular system (t-system) and the arrangement of associated proteins are central to the function of ventricular cardiomyocytes. Recently, Savio-Galimberti and collaborators used confocal imaging and digital image processing to characterize the geometry of t-system in rabbit ventricular cells [1]. The average diameter(More)