Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Oct:64:160-165.
doi: 10.1016/j.sbi.2020.07.001. Epub 2020 Aug 21.

Challenges in protein docking

Ilya A Vakser  1
Affiliations
Review

Challenges in protein docking

Ilya A Vakser. Curr Opin Struct Biol. 2020 Oct.

Abstract

Current developments in protein docking aim at improvement of applicability, accuracy and utility of modeling macromolecular complexes. The challenges include the need for greater emphasis on protein docking to molecules of different types, proper accounting for conformational flexibility upon binding, new promising methodologies based on residue co-evolution and deep learning, affinity prediction, and further development of fully automated docking servers. Importantly, new developments increasingly focus on realistic modeling of protein interactions in vivo, including crowded environment inside a cell, which involves multiple transient encounters, and propagating the system in time. This opinion paper offers the author's perspective on these challenges in structural modeling of protein interactions and the future of protein docking.

PubMed Disclaimer

Conflict of interest statement

Disclosure

The author declares no conflict of interest.

Figures

Figure 1
Figure 1
Challenges in protein docking.
Figure 2.
Figure 2.. Modeling representation of protein packing in cytosol.
The extremely tight packing of the proteins, which is close to physiological, illustrates the exceptional challenge of atomistic modeling of protein interactions in the crowded environment of the cell.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Vakser IA: Protein-protein docking: From interaction to interactome. Biophys. J. 2014, 107:1785–1793 - PMC - PubMed

    1. Pan AC, Jacobson D, Yatsenko K, Sritharan D, Weinreich TM, Shaw DE: Atomic-level characterization of protein-protein association. Proc. Nati. Acad. Sci. USA 2019, 116:4244–4249.

      • The paper describes molecular dynamics-based simulation of protein association. The molecular dynamics protocols, so far, have been unsuccessful in solving the general docking problem, due to the complexity of the system’s energy landscape. The paper appears to be the first successful application of the molecular dynamics-based simulation to protein docking, predicting the binding modes of several complexes, at the same time allowing exploration of the binding pathways.

    1. Garzon JI, Deng L, Murray D, Shapira S, Petrey D, Honig B: A computational interactome and functional annotation for the human proteome. eLife 2016, 5:e18715. - PMC - PubMed
    1. Kundrotas PJ, Zhu Z, Vakser IA: GWIDD: A comprehensive resource for genome-wide structural modeling of protein-protein interactions. Human Genomics 2012, 6:7. - PMC - PubMed
    1. Mosca R, Ceol A, Aloy P: Interactome3d: Adding structural details to protein networks. Nature Methods 2013, 10:47–53 - PubMed

Publication types

LinkOut - more resources