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Talk- Nikolai Smolin

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  • cmb seminar
When Oct 02, 2017
from 11:00 AM to 12:30 PM
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Dynamics of Health Related Proteins: from Heart to HIV

Protein dynamics is crucial for macromolecules biological functions. We are using molecular dynamics simulation approach to study properties of different health related biological systems. There are several key players in governing the relaxation and contraction of cardiac muscles. Here I would like to present our molecular dynamics simulation studies on some of them: sarcoplasmic reticulum (SR) calcium pump (SERCA), phospholamban (PLB), phospholemman (PLM) and cardiac Troponin complex. To characterize the conformational dynamics of sarcoplasmic reticulum (SR) calcium pump (SERCA) we performed molecular dynamics simulations beginning with several different high-resolution structures. We quantified differences in structural disorder and dynamics for an open conformation of SERCA versus closed structures, and observed that dynamic motions of SERCA cytoplasmic domains decreased with decreasing domain-domain separation distance.  The results are useful for interpretation of recent intramolecular Förster resonance energy transfer (FRET) distance measurements obtained for SERCA fused to fluorescent protein tags. Also, we performed MD simulations of mutants of PLB and PLM. The cardiac Troponin cTnI-R145W mutation is associated with restrictive cardiomyopathy (RCM). Molecular dynamics simulations revealed a marked reduction in interactions between Helix-C of cTnC (residues 56,59,63), and cTnI (residue 145) in the presence of either cTnI-RCM mutation or cTnI-PKC phosphomimetic. These results suggest that the RCM associated cTnI-R145W mutation induces a structural state that is similar, yet more extensive, to that induced by PKC mediated phosphorylation of cTnI-T143. Additionally, I will discuss some our results related to HIV restrictions by TRIM5α.

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