TY - JOUR T1 - Conformational Dynamics and Energy Landscapes of Ligand Binding in RyR1 JF - bioRxiv DO - 10.1101/167080 SP - 167080 AU - A. Dashti AU - D. Ben Hail AU - G. Mashayekhi AU - P. Schwander AU - A. des Georges AU - J. Frank AU - A. Ourmazd Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/07/21/167080.abstract N2 - Using experimental single-particle cryo-EM snapshots of ryanodine receptor (RyR1), a Ca2+-channel involved in skeletal muscle excitation/contraction coupling, we present quantitative free-energy landscapes, reaction coordinates, and three-dimensional movies of the continuous conformational changes associated with the binding of activating ligands. Our results show multiple routes to ligand binding with comparable branching ratios. All high-probability routes involve significant conformational changes before and after the binding of ligands. We also present new insights into the local structural changes along the ligand-binding route, including accommodations at the calcium, ATP, and caffeine binding sites. These observations shed new light on the mechanisms and conformational routes to ligand binding. ER -