Paper Citing NAMD - Abstract
Kumar, Amit; Chakravarty, Harapriya; Bal, Naresh C.; Balaraju, Tuniki; Jena, Nivedita; Misra, Gauri; Bal, Chandralata; Pieroni, Enrico; Periasamy, Muthu; Sharon, Ashoke
Identification of calcium binding sites on calsequestrin 1 and their implications for polymerization
MOLECULAR BIOSYSTEMS, 9:1949-1957, 2013
Biophysical studies have shown that each molecule of calsequestrin 1 (CASQ1) can bind about 70-80 Ca2+ ions. However, the nature of Ca2+-binding sites has not yet been fully characterized. In this study, we employed in silico approaches to identify the Ca2+ binding sites and to understand the molecular basis of CASQ1-Ca2+ recognition. We built the protein model by extracting the atomic coordinates for the back-to-back dimeric unit from the recently solved hexameric CASQ1 structure (PDB id: 3UOM) and adding the missing C-terminal residues (aa350-364). Using this model we performed extensive 30 ns molecular dynamics simulations over a wide range of Ca2+ concentrations ([Ca2+]). Our results show that the Ca2+-binding sites on CASQ1 differ both in affinity and geometry. The high affinity Ca2+-binding sites share a similar geometry and interestingly, the majority of them were found to be induced by increased [Ca2+]. We also found that the system shows maximal Ca2+-binding to the CAS (consecutive aspartate stretch at the C-terminus) before the rest of the CASQ1 surface becomes saturated. Simulated data show that the CASQ1 back-to-back stacking is progressively stabilized by the emergence of an increasing number of hydrophobic interactions with increasing [Ca2+]. Further, this study shows that the CAS domain assumes a compact structure with an increase in Ca2+ binding, which suggests that the CAS domain might function as a Ca2+-sensor that may be a novel structural motif to sense metal. We propose the term "Dn-motif'' for the CAS domain.
