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

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)

Melany Contreras (Creator)

Institution

East Carolina University (ECU )

Web Site: http://www.ecu.edu/lib/

Abstract: Toxic metals such as Cd and Pb present a threat to public health, as they can cause cognitive\r\ndisorders, various cancers, and heart disease through molecular ion mimicry. Divalent Cd2+ and\r\nPb2+ ions can bind to human cardiac troponin C (hcTnC), a Ca2+ binding protein responsible for\r\nheart muscle contraction, to cause Cd and Pb toxicity. The mechanism and the thermodynamics in\r\nwhich they bind to hcTnC, however, remain unclear. Molecular Dynamics (MD) simulations were\r\nperformed for hcTnC wild-type bound to Ca2+, Cd2+, and Pb2+ using AMBER 18 in order to obtain\r\nfree binding energies. This study suggests that Cd2+ and Pb2+ binding to hcTnC is\r\nthermodynamically favorable and that Cd2+ thermodynamically and structurally mimics Ca2+\r\nbinding to hcTnC. Furthermore, Cys residues located in positions 35 and 84 do not appear to\r\nparticipate in Cd2+ and Pb2+ coordination as they are at least 4 angstroms away from any metal ion.\r\nObtaining thermodynamic information on Cd2+ and Pb2+ binding to hcTnC may provide insight\r\ninto the basis of Cd and Pb metal toxicity.

Additional Information

Publication

Thesis

Language: English

Date: 2023

Subjects

molecular dynamics;metal toxicity

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