A stochastic roadmap method to model protein structural transitions. Issue 8 (11th December 2015)

• Record Type: Journal Article
• Authors: Molloy, Kevin; Clausen, Rudy; Shehu, Amarda
• Is Part Of: Robotica. Volume 34:Issue 8(2016)
• Page Start: 1705
• Page End: 1733
• Publication Date: 2015-12-11
• Subjects: Protein dynamics, -- Structural transitions, -- Conformational switching, -- SOD1 and Ras variants, -- Human disorders, -- Stochastic roadmap simulation, -- Markov state model, -- First-step analysis, -- Path smoothing, -- Energy landscape; Robots -- Periodicals; 629.89205
• DOI: 10.1017/S0263574715001058
• Languages: English
• ISSNs: 0263-5747

Abstract

SUMMARY: Evidence is emerging that the role of protein structure in disease needs to be rethought. Sequence mutations in proteins are often found to affect the rate at which a protein switches between structures. Modeling structural transitions in wildtype and variant proteins is central to understanding the molecular basis of disease. This paper investigates an efficient algorithmic realization of the stochastic roadmap simulation framework to model structural transitions in wildtype and variants of proteins implicated in human disorders. Our results indicate that the algorithm is able to extract useful information on the impact of mutations on protein structure and function.