2026-04-17T04:15:50Zhttps://recercat.cat/oai/request

oai:recercat.cat:2117/888222026-01-21T06:57:04Zcom_2072_1033col_2072_452950

00925njm 22002777a 4500 dc Gil, Victor A. author Lecina, Daniel author Grebner, Christoph author Guallar, Victor author 2016-07-04 Normal mode methods are becoming a popular alternative to sample the conformational landscape of proteins. In this study, we describe the implementation of an internal coordinate normal mode analysis method and its application in exploring protein flexibility by using the Monte Carlo method PELE. This new method alternates two different stages, a perturbation of the backbone through the application of torsional normal modes, and a resampling of the side chains. We have evaluated the new approach using two test systems, ubiquitin and c-Src kinase, and the differences to the original ANM method are assessed by comparing both results to reference molecular dynamics simulations. The results suggest that the sampled phase space in the internal coordinate approach is closer to the molecular dynamics phase space than the one coming from a Cartesian coordinate anisotropic network model. In addition, the new method shows a great speedup (∼∼5-7x), making it a good candidate for future normal mode implementations in Monte Carlo methods. The authors thank D. E. Shaw Research lab. for providing the kinase MD coordinates and Dr. López Blanco for sharing the code developed in his thesis and for providing useful comments. This work was supported by the CTQ-48287-R projects of the Spanish Ministry of Economy and Competitiveness (MINECO) and the grant SEV-2011-00067 of Severo Ochoa Program, awarded by the Spanish Government. Peer Reviewed Postprint (author's final draft) Àrees temàtiques de la UPC::Enginyeria biomèdica Protein engineering Protein Structure Simulation and Modeling Monte Carlo method Internal coordinates Normal Mode Analysis Monte Carlo Flexibility sampling Proteïnes--Enginyeria genètica Proteïnes--Estructura Enhancing backbone sampling in Monte Carlo simulations using Internal Coordinates Normal Mode Analysis