Abstract

Metal ions play an essential role in several cellular functions. Calcium is a ubiquitous regulator and is involved in numerous physiological processes. A class of proteins have evolved that sense calcium levels inside cells and act as effector molecules. Calmodulin is one such protein that gets activated after binding to calcium and thereafter interacts with its many targets. Calmodulin comprises two homologous domains that are connected by a flexible linker. The calcium-dependent flexibility of the linker results in numerous conformations of calmodulin. In this work using microsecond long MD simulations and well-tempered metadynamics, we explore how the calcium induced conformation dynamics of calmodulin is different from the inherent fluctuations of apocalmodulin and whether it has any role in preparing calmodulin for its interaction with its target-smooth muscle myosin light chain kinase (smMLCK). We have observed that calcium bound calmodulin could explore states that are predisposed toward peptide binding. We also found that though the binding of calmodulin to smMLCK peptide is calcium-independent, calcium regulates the domain to which the peptide will be bound. On the basis of our findings, we have proposed two alternate pathways for smMLCK peptide binding to calmodulin as directed by the ambient calcium concentrations. Our work proposes how calmodulin functions under physiologically dynamic calcium concentrations.

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.