Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Efficient consideration of coordinated water molecules improves computational protein-protein and protein-ligand docking

Ryan E. Pavlovicz, Hahnbeom Park, Frank DiMaio
doi: https://doi.org/10.1101/618603
Ryan E. Pavlovicz
aDepartment of Biochemistry, University of Washington, Seattle, WA 98195, United States
bInstitute for Protein Design, University of Washington, Seattle, WA 98195, United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hahnbeom Park
aDepartment of Biochemistry, University of Washington, Seattle, WA 98195, United States
bInstitute for Protein Design, University of Washington, Seattle, WA 98195, United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Frank DiMaio
aDepartment of Biochemistry, University of Washington, Seattle, WA 98195, United States
bInstitute for Protein Design, University of Washington, Seattle, WA 98195, United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: dimaio@u.washington.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

ABSTRACT

Highly-coordinated water molecules are frequently an integral part of protein-protein and protein-ligand interfaces. We introduce an updated energy model that efficiently captures the energetic effects of these highly-coordinated water molecules on the surfaces of proteins. A two-stage protocol is developed in which polar groups arranged in geometries suitable for water placement are first identified, then a modified Monte Carlo simulation allows highly coordinated waters to be placed on the surface of a protein while simultaneously sampling amino acid side chain orientations. This “semi-explicit” water model is implemented in Rosetta and is suitable for both structure prediction and protein design. We show that our new approach and energy - model yield significant improvements in native structure recovery of protein-protein and protein-ligand docking.

Footnotes

  • Figure 1 expanded to show potentials of implicit water score. Benchmarking performed against 3D-RISM as implemented in AmberTools (results briefly mentioned in main text, with detailed results in Supplement) Additional clarifying statements made throughout.

  • ABBREVIATIONS

    Rosetta-ICO
    implicit consideration of coordinated water
    Rosetta-ECO
    explicit consideration of coordinated water
    PPI
    protein-protein interface
    RMSD
    root-mean-square deviation
  • Copyright 
    The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
    Back to top
    PreviousNext
    Posted July 29, 2019.
    Download PDF
    Email

    Thank you for your interest in spreading the word about bioRxiv.

    NOTE: Your email address is requested solely to identify you as the sender of this article.

    Enter multiple addresses on separate lines or separate them with commas.
    Efficient consideration of coordinated water molecules improves computational protein-protein and protein-ligand docking
    (Your Name) has forwarded a page to you from bioRxiv
    (Your Name) thought you would like to see this page from the bioRxiv website.
    CAPTCHA
    This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
    Share
    Efficient consideration of coordinated water molecules improves computational protein-protein and protein-ligand docking
    Ryan E. Pavlovicz, Hahnbeom Park, Frank DiMaio
    bioRxiv 618603; doi: https://doi.org/10.1101/618603
    Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
    Citation Tools
    Efficient consideration of coordinated water molecules improves computational protein-protein and protein-ligand docking
    Ryan E. Pavlovicz, Hahnbeom Park, Frank DiMaio
    bioRxiv 618603; doi: https://doi.org/10.1101/618603

    Citation Manager Formats

    • BibTeX
    • Bookends
    • EasyBib
    • EndNote (tagged)
    • EndNote 8 (xml)
    • Medlars
    • Mendeley
    • Papers
    • RefWorks Tagged
    • Ref Manager
    • RIS
    • Zotero
    • Tweet Widget
    • Facebook Like
    • Google Plus One

    Subject Area

    • Biochemistry
    Subject Areas
    All Articles
    • Animal Behavior and Cognition (3602)
    • Biochemistry (7567)
    • Bioengineering (5522)
    • Bioinformatics (20782)
    • Biophysics (10325)
    • Cancer Biology (7978)
    • Cell Biology (11635)
    • Clinical Trials (138)
    • Developmental Biology (6602)
    • Ecology (10200)
    • Epidemiology (2065)
    • Evolutionary Biology (13611)
    • Genetics (9539)
    • Genomics (12844)
    • Immunology (7919)
    • Microbiology (19538)
    • Molecular Biology (7657)
    • Neuroscience (42081)
    • Paleontology (308)
    • Pathology (1257)
    • Pharmacology and Toxicology (2201)
    • Physiology (3267)
    • Plant Biology (7038)
    • Scientific Communication and Education (1294)
    • Synthetic Biology (1951)
    • Systems Biology (5426)
    • Zoology (1116)