atomic interaction networks in the core of protein domains and their native folds原子相互作用网络的核心蛋白质域和本国折叠.pdfVIP

Atomic Interaction Networks in the Core of Protein Domains and Their Native Folds Venkataramanan Soundararajan, Rahul Raman, S. Raguram, V. Sasisekharan, Ram Sasisekharan* Harvard-MIT Division of Health Sciences Technology, Koch Institute for Integrative Cancer Research and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America Abstract Vastly divergent sequences populate a majority of protein folds. In the quest to identify features that are conserved within protein domains belonging to the same fold, we set out to examine the entire protein universe on a fold-by-fold basis. We report that the atomic interaction network in the solvent-unexposed core of protein domains are fold-conserved, extraordinary sequence divergence notwithstanding. Further, we find that this feature, termed protein core atomic interaction network (or PCAIN) is significantly distinguishable across different folds, thus appearing to be ‘‘signature’’ of a domain’s native fold. As part of this study, we computed the PCAINs for 8698 representative protein domains from families across the 1018 known protein folds to construct our seed database and an automated framework was developed for PCAIN-based characterization of the protein fold universe. A test set of randomly selected domains that are not in the seed database was classified with over 97% accuracy, independent of sequence divergence. As an application of this novel fold signature, a PCAIN-based scoring scheme was developed for comparative (homology-based) structure prediction, with 1–2 angstroms (mean 1.61A) Ca RMSD generally observed between computed structures and reference crystal structures. Our results are consistent across the full spectrum of test domains including those from rec