Paper Citing NAMD - Abstract
Kekenes-Huskey, Peter M.; Metzger, Vincent T.; Grant, Barry J.; McCammon, J. Andrew
Calcium binding and allosteric signaling mechanisms for the sarcoplasmic reticulum Ca2+ATPase
PROTEIN SCIENCE, 21:1429-1443, OCT 2012
The sarcoplasmic reticulum Ca2+ ATPase (SERCA) is a membrane-bound pump that utilizes ATP to drive calcium ions from the myocyte cytosol against the higher calcium concentration in the sarcoplasmic reticulum. Conformational transitions associated with Ca2+-binding are important to its catalytic function. We have identified collective motions that partition SERCA crystallographic structures into multiple catalytically-distinct states using principal component analysis. Using Brownian dynamics simulations, we demonstrate the important contribution of surface-exposed, polar residues in the diffusional encounter of Ca2+. Molecular dynamics simulations indicate the role of Glu309 gating in binding Ca2+, as well as subsequent changes in the dynamics of SERCA's cytosolic domains. Together these data provide structural and dynamical insights into a multistep process involving Ca2+ binding and catalytic transitions.
