Link to the University of Pittsburgh Homepage
Link to the University Library System Homepage Link to the Contact Us Form

Exploring the Conformational Transitions of Biomolecular Systems Using a Simple Two-State Anisotropic Network Model

Das, A and Gur, M and Cheng, MH and Jo, S and Bahar, I and Roux, B (2014) Exploring the Conformational Transitions of Biomolecular Systems Using a Simple Two-State Anisotropic Network Model. PLoS Computational Biology, 10 (4). ISSN 1553-734X

[img]
Preview
PDF
Published Version
Available under License : See the attached license file.

Download (8MB) | Preview
[img] Plain Text (licence)
Available under License : See the attached license file.

Download (1kB)

Abstract

Biomolecular conformational transitions are essential to biological functions. Most experimental methods report on the long-lived functional states of biomolecules, but information about the transition pathways between these stable states is generally scarce. Such transitions involve short-lived conformational states that are difficult to detect experimentally. For this reason, computational methods are needed to produce plausible hypothetical transition pathways that can then be probed experimentally. Here we propose a simple and computationally efficient method, called ANMPathway, for constructing a physically reasonable pathway between two endpoints of a conformational transition. We adopt a coarse-grained representation of the protein and construct a two-state potential by combining two elastic network models (ENMs) representative of the experimental structures resolved for the endpoints. The two-state potential has a cusp hypersurface in the configuration space where the energies from both the ENMs are equal. We first search for the minimum energy structure on the cusp hypersurface and then treat it as the transition state. The continuous pathway is subsequently constructed by following the steepest descent energy minimization trajectories starting from the transition state on each side of the cusp hypersurface. Application to several systems of broad biological interest such as adenylate kinase, ATP-driven calcium pump SERCA, leucine transporter and glutamate transporter shows that ANMPathway yields results in good agreement with those from other similar methods and with data obtained from all-atom molecular dynamics simulations, in support of the utility of this simple and efficient approach. Notably the method provides experimentally testable predictions, including the formation of non-native contacts during the transition which we were able to detect in two of the systems we studied. An open-access web server has been created to deliver ANMPathway results. © 2014 Das et al.


Share

Citation/Export:
Social Networking:
Share |

Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Das, A
Gur, Mmeg78@pitt.eduMEG78
Cheng, MH
Jo, S
Bahar, Ibahar@pitt.eduBAHAR
Roux, B
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
Editorde Groot, Bert L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 1 January 2014
Date Type: Publication
Journal or Publication Title: PLoS Computational Biology
Volume: 10
Number: 4
DOI or Unique Handle: 10.1371/journal.pcbi.1003521
Schools and Programs: School of Medicine > Computational and Systems Biology
Refereed: Yes
ISSN: 1553-734X
Date Deposited: 01 Jul 2014 17:50
Last Modified: 04 Feb 2019 15:57
URI: http://d-scholarship.pitt.edu/id/eprint/22181

Metrics

Monthly Views for the past 3 years

Plum Analytics

Altmetric.com


Actions (login required)

View Item View Item