Referenced in: none

Automatically associated channels: Kir2.3

Title: Generation, comparison, and merging of pathways between protein conformations: gating in K-channels.

Authors: Angela Enosh, Barak Raveh, Ora Furman-Schueler, Dan Halperin, Nir Ben-Tal

Journal, date & volume: Biophys. J., 2008 Oct , 95, 3850-60

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/18621834

Abstract
We present a general framework for the generation, alignment, comparison, and hybridization of motion pathways between two known protein conformations. The framework, which is rooted in probabilistic motion-planning techniques in robotics, allows for the efficient generation of collision-free motion pathways, while considering a wide range of degrees of freedom involved in the motion. Within the framework, we provide the means to hybridize pathways, thus producing, the motion pathway of the lowest energy barrier out of the many pathways proposed by our algorithm. This method for comparing and hybridizing pathways is modular, and may be used within the context of molecular dynamics and Monte Carlo simulations. The framework was implemented within the Rosetta software suite, where the protein is represented in atomic detail. The K-channels switch between open and closed conformations, and we used the overall framework to investigate this transition. Our analysis suggests that channel-opening may follow a three-phase pathway. First, the channel unlocks itself from the closed state; second, it opens; and third, it locks itself in the open conformation. A movie that depicts the proposed pathway is available in the Supplementary Material (Movie S1) and at http://www.cs.tau.ac.il/~angela/SuppKcsA.html.