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IDP-LZerD: Intrinsically Disordered Protein Docking

Download IDP-LZerD from GitHub.

Introduction

Disordered protein-protein interactions (disordered PPIs), which involve an intrinsically disordered protein (IDP) are typically considered outside the scope of conventional docking. Protein-peptide docking methods exist, but they are generally designed for very short protein chains. IDP-LZerD, our disordered PPI modeling method, follows the dock-and-coalesce model of disordered PPI formation. The problem is brought within the scope of conventional docking by initially docking IDP fragments to the receptor, followed by a combinatorial path search and model refinement. IDP-LZerD has been demonstrated to work on IDPs up to 69 residues long.

Inputs

IDP-LZerD requires the sequence of the IDP to be modeled and a PDB-format model of the receptor structure. The receptor model can be either an unbound or bound structure. IDP-LZerD also accepts secondary structure prediction methods, and it is recommended to input any confident secondary structure information available. Example of secondary structure prediction methods include:

  • PSIPRED (available at http://bioinf.cs.ucl.ac.uk/psipred/)
  • JPRED (available at http://www.compbio.dundee.ac.uk/jpred/)
  • Porter (available at http://distillf.ucd.ie/porterpaleale/)
  • SSPro (available at http://scratch.proteomics.ics.uci.edu/)
  • DeepCNF/RaptorX Property (available at http://raptorx.uchicago.edu/StructurePropertyPred/predict/)
  • SPIDER3 (available at http://sparks-lab.org/server/SPIDER3/)
  • DNSS (available at http://sysbio.rnet.missouri.edu/multicom_toolbox/tools.html)

Outputs

IDP-LZerD outputs full-atom models of the disordered PPI.

Methods

Figure 1. IDP-LZerD consists of four steps.
1. fragment structure prediction, 2. fragment docking, 3. path assembly, and 4. refinement. Steps 1 and 2 correspond to “dock” and Steps 3 and 4 correspond to “coalesce.” This figure is taken from Figure 1 of the original IDP-LZerD paper [1] (available under the Creative Commons CC0 public domain dedication).

Figure 2. Programs and input data to use for each step in IDP-LZerD.

The above figures show the general flow of IDP-LZerD. Given a receptor structure and an IDP sequence, full-atom fragment models of the IDP are generated using the Rosetta fragment picker, possibly including secondary structure information from secondary structure prediction methods or from the literature. Then, our protein-protein docking software, LZerD, is used to dock the fragment models to the receptor. The docked fragments are then combinatorially assembled into full-chain models, and are then finally refined using a short molecular dynamics simulation.

References

If you use IDP-LZerD, please cite:

  1. Lenna X Peterson, Amitava Roy, Charles Christoffer, Genki Terashi, and Daisuke Kihara. Modeling disordered protein interactions from biophysical principles. PLoS Computational Biology 13: e1005485(2017)

   
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