ArticleThe journal of physical chemistry. B2011
A computational and experimental approach to investigate bepridil binding with cardiac troponin.
Article in The journal of physical chemistry. B, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- Hypertrophic Cardiomyopathy Mutations of Troponin Reveal Details of Striated Muscle Regulation.Frontiers in physiology · 2022Pooled it
- Umbrella Sampling Simulations of Cardiac Thin Filament Reveal Thermodynamic Consequences of Troponin I Inhibitory Peptide Mutations.Journal of chemical information and modeling · 2023Article
- Large scale peptide screening against main protease of SARS CoV-2.Journal of computational chemistry · 2023Article
- Umbrella Sampling Simulations Measure Switch Peptide Binding and Hydrophobic Patch Opening Free Energies in Cardiac Troponin.Journal of chemical information and modeling · 2022Article
- Discovery of Novel Small-Molecule Calcium Sensitizers for Cardiac Troponin C: A Combined Virtual and Experimental Screening Approach.Journal of chemical information and modeling · 2020Article
- Mechanism of Cardiac Troponin C Calcium Sensitivity Modulation by Small Molecules Illuminated by Umbrella Sampling Simulations.Journal of chemical information and modeling · 2019Article
- 3-Chlorodiphenylamine activates cardiac troponin by a mechanism distinct from bepridil or TFP.The Journal of general physiology · 2019Article
- Computational Studies of Cardiac and Skeletal Troponin.Frontiers in molecular biosciences · 2019Review
- Molecular Dynamics and Umbrella Sampling Simulations Elucidate Differences in Troponin C Isoform and Mutant Hydrophobic Patch Exposure.The journal of physical chemistry. B · 2018Article
- Molecular Effects of cTnC DCM Mutations on Calcium Sensitivity and Myofilament Activation-An Integrated Multiscale Modeling Study.The journal of physical chemistry. B · 2016Article
- Cardiac troponin structure-function and the influence of hypertrophic cardiomyopathy associated mutations on modulation of contractility.Archives of biochemistry and biophysics · 2016Review
- Fluorescence Based Characterization of Calcium Sensitizer Action on the Troponin Complex.Chemical biology & drug design · 2016Article
- Effects of HCM cTnI mutation R145G on troponin structure and modulation by PKA phosphorylation elucidated by molecular dynamics simulations.Biophysical journal · 2015Article
- Computational studies of the effect of the S23D/S24D troponin I mutation on cardiac troponin structural dynamics.Biophysical journal · 2014Article
- Thermodynamics and molecular dynamics simulations of calcium binding to the regulatory site of human cardiac troponin C: evidence for communication with the structural calcium binding sites.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2013Article
- Disease causing mutations of troponin alter regulated actin state distributions.Journal of muscle research and cell motility · 2012Review
- Molecular effects of familial hypertrophic cardiomyopathy-related mutations in the TNT1 domain of cTnT.Journal of molecular biology · 2012Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Cardiac troponin is a Ca(2+)-dependent switch for the contraction in heart muscle and a potential target for drugs in the therapy of heart failure. Bepridil is a drug that binds to troponin and increases calcium sensitivity of muscle contraction. Because bepridil has been well studied, it is a good model for analysis by computational and experimental methods. Molecular dynamics (MD) simulations were performed on troponin complexes of different sizes in the presence and absence of bepridil bound within the hydrophobic pocket at the N-terminal domain of troponin C. About 100 ns of simulation trajectory data were generated, which were analyzed using cross-correlation analyses and MMPBSA and MMGBSA techniques. The results indicated that bepridil binding within the hydrophobic pocket of cardiac TnC decreases the interaction of TnC with TnI at both the N-domain of TnC and the C-domain of TnC, and decreases the correlations of motions among the segments of the troponin subunits. The estimated calcium-binding affinities using MMPBSA showed that bepridil has a sensitizing effect for the isolated system of TnC, but loses this effect for the complex. Our experimental measurements of calcium dissociation rates were consistent with that prediction. We also observed that while bepridil enhanced the troponin-tropomyosin-actin-activated ATPase activity of myosin S1 at low calcium concentrations it was slightly inhibitory at high calcium concentrations. Bepridil increases the ATPase activity and force generation in muscle fibers, but its effects appear to depend on the concentration of calcium.
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