Addressing the Role of Conformational Diversity in Protein Structure Prediction.

ABSTRACT: Computational modeling of tertiary structures has become of standard use to study proteins that lack experimental characterization. Unfortunately, 3D structure prediction methods and model quality assessment programs often overlook that an ensemble of conformers in equilibrium populates the native state of proteins. In this work we collected sets of publicly available protein models and the corresponding target structures experimentally solved and studied how they describe the conformational diversity of the protein. For each protein, we assessed the quality of the models against known conformers by several standard measures and identified those models ranked best. We found that model rankings are defined by both the selected target conformer and the similarity measure used. 70% of the proteins in our datasets show that different models are structurally closest to different conformers of the same protein target. We observed that model building protocols such as template-based or ab initio approaches describe in similar ways the conformational diversity of the protein, although for template-based methods this description may depend on the sequence similarity between target and template sequences. Taken together, our results support the idea that protein structure modeling could help to identify members of the native ensemble, highlight the importance of considering conformational diversity in protein 3D quality evaluations and endorse the study of the variability of the native structure for a meaningful biological analysis.

SUBMITTER: Palopoli N 

PROVIDER: S-EPMC4861349 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature