Cardiac myosin binding protein-C (cMyBP-C) is a multi-domain (C0–C10) protein that regulates heart muscle contraction
through interaction with myosin, actin and other sarcomeric proteins. Several mutations of this protein cause familial
hypertrophic cardiomyopathy (HCM). Domain C1 of cMyBP-C plays a central role in protein interactions with actin and
myosin. Here, we studied structure-function relationship of three disease causing mutations, Arg177His, Ala216Thr and
Glu258Lys of the domain C1 using computational biology techniques with its available X-ray crystal structure. The results
suggest that each mutation could affect structural properties of the domain C1, and hence it’s structural integrity through
modifying intra-molecular arrangements in a distinct mode. The mutations also change surface charge distributions, which
could impact the binding of C1 with other sarcomeric proteins thereby affecting contractile function. These structural
consequences of the C1 mutants could be valuable to understand the molecular mechanisms for the disease.