Protein-RNA complexes and efficient automatic docking: expanding RosettaDock possibilities

PLoS One. 2014 Sep 30;9(9):e108928. doi: 10.1371/journal.pone.0108928. eCollection 2014.

Abstract

Protein-RNA complexes provide a wide range of essential functions in the cell. Their atomic experimental structure solving, despite essential to the understanding of these functions, is often difficult and expensive. Docking approaches that have been developed for proteins are often challenging to adapt for RNA because of its inherent flexibility and the structural data available being relatively scarce. In this study we adapted the RosettaDock protocol for protein-RNA complexes both at the nucleotide and atomic levels. Using a genetic algorithm-based strategy, and a non-redundant protein-RNA dataset, we derived a RosettaDock scoring scheme able not only to discriminate but also score efficiently docking decoys. The approach proved to be both efficient and robust for generating and identifying suitable structures when applied to two protein-RNA docking benchmarks in both bound and unbound settings. It also compares well to existing strategies. This is the first approach that currently offers a multi-level optimized scoring approach integrated in a full docking suite, leading the way to adaptive fully flexible strategies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Area Under Curve
  • Hydrogen Bonding
  • Molecular Docking Simulation
  • Nucleic Acid Conformation
  • Protein Binding
  • Protein Structure, Tertiary
  • Proteins / chemistry
  • Proteins / metabolism*
  • RNA / chemistry
  • RNA / metabolism*
  • ROC Curve
  • Software*

Substances

  • Proteins
  • RNA

Grants and funding

This work was granted access to the HPC resources of TGCC (Très Grand Centre de calcul du CEA - http://www-hpc.cea.fr/en/complexe/tgcc-curie.htm) under the allocation t2013077065 made by GENCI (Grand Equipement National de Calcul Intensif - http://www.genci.fr). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.