Enhancing backbone sampling in Monte Carlo simulations using internal coordinates normal mode analysis. Issue 20 (15th October 2016)

• Record Type: Journal Article
• Authors: Gil, Victor A.; Lecina, Daniel; Grebner, Christoph; Guallar, Victor
• Is Part Of: Bioorganic & medicinal chemistry. Volume 24:Issue 20(2016)
• Page Start: 4855
• Page End: 4866
• Publication Date: 2016-10-15
• Subjects: Internal coordinates -- Normal mode analysis -- Monte Carlo -- Flexibility sampling; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2016.07.001
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: 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 (∼5–7×), making it a good candidate for future normal mode implementations in Monte Carlo methods.