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BMC Bioinformatics

, 18:271

Structural analysis


BackgroundEssential Dynamics ED is a common application of principal component analysis PCA to extract biologically relevant motions from atomic trajectories of proteins. Covariance and correlation based PCA are two common approaches to determine PCA modes eigenvectors and their eigenvalues. Protein dynamics can be characterized in terms of Cartesian coordinates or internal distance pairs. In understanding protein dynamics, a comparison of trajectories taken from a set of proteins for similarity assessment provides insight into conserved mechanisms. Comprehensive software is needed to facilitate comparative-analysis with user-friendly features that are rooted in best practices from multivariate statistics.

ResultsWe developed a Java based Essential Dynamics toolkit called JED to compare the ED from multiple protein trajectories. Trajectories from different simulations and different proteins can be pooled for comparative studies. JED implements Cartesian-based coordinates cPCA and internal distance pair coordinates dpPCA as options to construct covariance Q or correlation R matrices. Statistical methods are implemented for treating outliers, benchmarking sampling adequacy, characterizing the precision of Q and R, and reporting partial correlations. JED output results as text files that include transformed coordinates for aligned structures, several metrics that quantify protein mobility, PCA modes with their eigenvalues, and displacement vector DV projections onto the top principal modes. Pymol scripts together with PDB files allow movies of individual Q- and R-cPCA modes to be visualized, and the essential dynamics occurring within user-selected time scales. Subspaces defined by the top eigenvectors are compared using several statistical metrics to quantify similarity-overlap of high dimensional vector spaces. Free energy landscapes can be generated for both cPCA and dpPCA.

ConclusionsJED offers a convenient toolkit that encourages best practices in applying multivariate statistics methods to perform comparative studies of essential dynamics over multiple proteins. For each protein, Cartesian coordinates or internal distance pairs can be employed over the entire structure or user-selected parts to quantify similarity-differences in mobility and correlations in dynamics to develop insight into protein structure-function relationships.

KeywordsEssential dynamics Principal component analysis Distance pairs Partial correlations Vector space comparison Principal angles AbbreviationscPCACartesian Principal component analysis

dpPCADistance pair Principal component analysis

DVDisplacement vectors

JEDJava Essential Dynamics

PPartial Correlation matrix

PC1Principal component 1

PC2Principal component 2

PC3Principal component 3

QCovariance Matrix

RCorrelation matrix

Electronic supplementary materialThe online version of this article doi:10.1186-s12859-017-1676-y contains supplementary material, which is available to authorized users.

Autor: Charles C. David - Ettayapuram Ramaprasad Azhagiya Singam - Donald J. Jacobs


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