Mapping Ryanodine Binding Sites in the Pore Cavity of Ryanodine Receptors.

ABSTRACT: Ryanodine (Ryd) irreversibly targets ryanodine receptors (RyRs), a family of intracellular calcium release channels essential for many cellular processes ranging from muscle contraction to learning and memory. Little is known of the atomistic details about how Ryd binds to RyRs. In this study, we used all-atom molecular dynamics simulations with both enhanced and bidirectional sampling to gain direct insights into how Ryd interacts with major residues in RyRs that were experimentally determined to be critical for its binding. We found that the pyrrolic ring of Ryd displays preference for the R⁴⁸⁹²AGGG-F⁴⁹²¹ residues in the cavity of RyR1, which explain the effects of the corresponding mutations in RyR2 in experiments. Particularly, the mutant Q4933A (or Q4863A in RyR2

SUBMITTER: Ngo VA 

PROVIDER: S-EPMC5406381 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature