TopProperty: Robust Metaprediction of Transmembrane and Globular Protein Features Using Deep Neural Networks.

Journal: Journal of chemical theory and computation
Published Date:

Abstract

Transmembrane proteins (TMPs) are critical components of cellular life. However, due to experimental challenges, the number of experimentally resolved TMP structures is severely underrepresented in databases compared to their cellular abundance. Prediction of (per-residue) features such as transmembrane topology, membrane exposure, secondary structure, and solvent accessibility can be a useful starting point for experimental design or protein structure prediction but often requires different computational tools for different features or types of proteins. We present TopProperty, a metapredictor that predicts all of these features for TMPs or globular proteins. TopProperty is trained on datasets without bias toward a high number of sequence homologs, and the predictions are significantly better than the evaluated state-of-the-art primary predictors on all quality metrics. TopProperty eliminates the need for protein type- or feature-tailored tools, specifically for TMPs. TopProperty is freely available as a web server and standalone at https://cpclab.uni-duesseldorf.de/topsuite/.

Authors

  • Daniel Mulnaes
    Department of Mathematics and Natural Sciences , Institute for Pharmaceutical and Medicinal Chemistry, Heinrich Heine University Düsseldorf , Universitätsstrasse 1 , 40225 Düsseldorf , Germany.
  • Stephan Schott-Verdugo
    John von Neumann Institute for Computing (NIC), Jülich Supercomputing Centre (JSC), Institute of Biological Information Processing (IBI-7: Structural Bioinformatics), and Institute of Bio- and Geosciences (IBG-4: Bioinformatics), Forschungszentrum Jülich GmbH, Wilhelm-Johnen-Str., Jülich 52425, Germany.
  • Filip Koenig
    Institut für Pharmazeutische und Medizinische Chemie, Heinrich-Heine-Universität Düsseldorf, 40225 Düsseldorf, Germany.
  • Holger Gohlke
    Institute for Pharmaceutical and Medicinal Chemistry, Heinrich Heine University Düsseldorf 40225 Düsseldorf, Germany; Institute of Bio- and Geosciences (IBG4: Bioinformatics), Forschungszentrum Jülich GmbH, 52425 Jülich, Germany. Electronic address: gohlke@hhu.de.