MOLECULAR DYNAMICS STUDY OF DIVALENT CADMIUM AND LEAD BOUND TO HUMAN CARDIAC TROPONIN C (WT CYS 35, 84)

Abstract

Toxic metals such as Cd and Pb present a threat to public health, as they can cause cognitive disorders, various cancers, and heart disease through molecular ion mimicry. Divalent Cd2+ and Pb2+ ions can bind to human cardiac troponin C (hcTnC), a Ca2+ binding protein responsible for heart muscle contraction, to cause Cd and Pb toxicity. The mechanism and the thermodynamics in which they bind to hcTnC, however, remain unclear. Molecular Dynamics (MD) simulations were performed for hcTnC wild-type bound to Ca2+, Cd2+, and Pb2+ using AMBER 18 in order to obtain free binding energies. This study suggests that Cd2+ and Pb2+ binding to hcTnC is thermodynamically favorable and that Cd2+ thermodynamically and structurally mimics Ca2+ binding to hcTnC. Furthermore, Cys residues located in positions 35 and 84 do not appear to participate in Cd2+ and Pb2+ coordination as they are at least 4 angstroms away from any metal ion. Obtaining thermodynamic information on Cd2+ and Pb2+ binding to hcTnC may provide insight into the basis of Cd and Pb metal toxicity.