Recovering bound forms of Protein structures using the Elastic Network Model and Molecular Interaction Fields

Dario Ghersi, Roberto Sanchez

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

Proteins can undergo large conformational changes upon ligand binding. Knowledge of the bound form of a protein is critical for many computational applications, ranging from the functional characterization of proteins to drug discovery. However, traditional approaches like Molecular Dynamics or Monte Carlo simulations are computationally intensive and are often not suitable to capture large scale, collective conformational changes. To address this problem, we combine the Elastic Network Model to rapidly generate ensembles of conformations and a Molecular Interaction Fields approach to select conformations that closely resemble the bound form. Molecular Interaction Fields are a class of energy-based methods that characterize a protein structure using virtual chemical probes, yielding 3D maps of the interaction energy profile of the protein. As a proof of concept, we illustrate the use of our computational pipeline on a dataset of 11 structures that undergo large conformational changes upon binding. The results indicate that overall our method is capable of returning conformations that are significantly much closer to the bound form than the initial unbound conformations.

Original languageEnglish (US)
Title of host publicationACM-BCB 2016 - 7th ACM Conference on Bioinformatics, Computational Biology, and Health Informatics
PublisherAssociation for Computing Machinery, Inc
Pages50-57
Number of pages8
ISBN (Electronic)9781450342254
DOIs
Publication statusPublished - Oct 2 2016
Event7th ACM Conference on Bioinformatics, Computational Biology, and Health Informatics, ACM-BCB 2016 - Seattle, United States
Duration: Oct 2 2016Oct 5 2016

Publication series

NameACM-BCB 2016 - 7th ACM Conference on Bioinformatics, Computational Biology, and Health Informatics

Other

Other7th ACM Conference on Bioinformatics, Computational Biology, and Health Informatics, ACM-BCB 2016
CountryUnited States
CitySeattle
Period10/2/1610/5/16

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Keywords

  • Conformational changes
  • Elastic networks
  • Molecular Interaction Fields
  • Structural bioinformatics

ASJC Scopus subject areas

  • Software
  • Health Informatics
  • Biomedical Engineering
  • Computer Science Applications

Cite this

Ghersi, D., & Sanchez, R. (2016). Recovering bound forms of Protein structures using the Elastic Network Model and Molecular Interaction Fields. In ACM-BCB 2016 - 7th ACM Conference on Bioinformatics, Computational Biology, and Health Informatics (pp. 50-57). (ACM-BCB 2016 - 7th ACM Conference on Bioinformatics, Computational Biology, and Health Informatics). Association for Computing Machinery, Inc. https://doi.org/10.1145/2975167.2975172