Article
Molecular Effects of cTnC DCM Mutations on Calcium Sensitivity and Myofilament Activation-An Integrated Multiscale Modeling Study.
The journal of physical chemistry. B - 25 Aug 2016
Dewan Sukriti, McCabe Kimberly J, Regnier Michael, McCulloch Andrew D, Lindert Steffen
Abstract excerpt
Mutations in cardiac troponin C (D75Y, E59D, and G159D), a key regulatory protein of myofilament contraction, have been associated with dilated cardiomyopathy (DCM). Despite reports of altered myofilament function in these mutants, the underlying molecular alterations caused by these mutations remain elusive. Here we investigate in silico the intramolecular mechanisms by which these mutations affect myofilament...
Topics
- Amino Acid Sequence
- Amino Acid Substitution
- Animals
- Binding Sites
- Calcium
- Cardiomyopathy, Hypertrophic
- Crystallography, X-Ray
- Humans
- Hydrophobic and Hydrophilic Interactions
- Markov Chains
- Molecular Dynamics Simulation
- Mutation
- Myocardial Contraction