ProDy: protein dynamics inferred from theory and experiments

Abstract

Summary: We developed a Python package, ProDy, for structure-based analysis of protein dynamics. ProDy allows for quantitative characterization of structural variations in heterogeneous datasets of structures experimentally resolved for a given biomolecular system, and for comparison of these variations with the theoretically predicted equilibrium dynamics. Datasets include structural ensembles for a given family or subfamily of proteins, their mutants and sequence homologues, in the presence/absence of their substrates, ligands or inhibitors. Numerous helper functions enable comparative analysis of experimental and theoretical data, and visualization of the principal changes in conformations that are accessible in different functional states. ProDy application programming interface (API) has been designed so that users can easily extend the software and implement new methods.

Availability: ProDy is open source and freely available under GNU General Public License from http://www.csb.pitt.edu/ProDy/.

Fig. 1.

Comparative analysis of p38 dynamics from experiments (PCA) and theory (ANM). (A) Overlay of 150 p38 X-ray structures using ProDy. An inhibitor is shown in space-filling representation. (B) Network model (ANM) representation of p38 (generated using NMWiz and VMD). (C) Comparison of the principal mode PC1 (from experiments; violet arrows) and the softest mode ANM1 from theory (green arrows) and (D) overlap of the top five modes. (E) Distribution of X-ray structures (blue) and ANM-generated conformers (red) in the subspace spanned by PC1-3. The green ellipsoid is an analytical solution predicted by the ANM.