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 Cd and Pb ions can bind to human cardiac troponin C (hcTnC), a Ca(II) 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 Ca(II), Cd(II), and Pb(II) using AMBER 18 in order to obtain binding energies. This study suggests that Cd(II) and Pb(II) binding to the native Ca(II) binding sites in hcTnC wild-type may be enthalpically driven. Furthermore, Cys residues located in positions 35 and 84 do not appear to participate in Cd(II) coordination as they are either 4.9 (Figure 1, Left) or 20 angstroms away from Cd(II) ions. Obtaining thermodynamic information on divalent Cd and Pb metal binding to hcTnC may provide insight into the basis of Cd and Pb metal toxicity.

MD simulation study of Cd and Pb bound to human cardiac troponin C

ACS Spring Meeting 2021

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