Abstract
The Protein Data Bank (PDB) undergoes an exponential expansion in terms of the number of macromolecular structures deposited every year. A pivotal question is how this rapid growth of structural information improves the quality of three-dimensional models constructed by contemporary bioinformatics approaches. To address this problem, we performed a retrospective analysis of the structural coverage of a representative set of proteins using remote homology detected by COMPASS and HHpred. We show that the number of proteins whose structures can be confidently predicted increased during a 9-year period between 2005 and 2014 on account of the PDB growth alone. Nevertheless, this encouraging trend slowed down noticeably around the year 2008 and has yielded insignificant improvements ever since. At the current pace, it is unlikely that the protein structure prediction problem will be solved in the near future using existing template-based modeling techniques. Therefore, further advances in experimental structure determination, qualitatively better approaches in fold recognition, and more accurate template-free structure prediction methods are desperately needed.
Acknowledgments
Portions of this research were conducted with high-performance computational resources provided by the Louisiana State University (HPC@LSU; http://www.hpc.lsu.edu) and the Louisiana Optical Network Institute (LONI; http://www.loni.org). We thank Dr. Wei Feinstein who read the manuscript and provided critical comments.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: This work was supported by the Louisiana Board of Regents through the Board of Regents Support Fund [contract LEQSF(2012-15)-RD-A-05].
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
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