z-logo
Premium
An enhanced elastic network model to represent the motions of domain‐swapped proteins
Author(s) -
Song Guang,
Jernigan Robert L.
Publication year - 2006
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.20836
Subject(s) - infinitesimal , domain (mathematical analysis) , rigidity (electromagnetism) , displacement (psychology) , statistical physics , computer science , hinge , scale (ratio) , biological system , algorithm , physics , mathematics , classical mechanics , mathematical analysis , psychology , quantum mechanics , psychotherapist , biology
Domain swapping is a process where two (or more) protein molecules form a dimer (or higher oligomer) by exchanging an identical domain. In this article, based on the observation that domains are rigid and hinge loops are highly flexible, we propose a new Elastic Network Model, domain‐ENM, for domain‐swapped proteins. In this model, the rigidity of domains is taken into account by using a larger spring constant for intradomain contacts. The large‐scale transition of domain swapping is then novelly decomposed into the relative motion between the rigid domains (only 6 degrees of freedom) plus the internal fluctuations of each domain. Consequently, this approach has the potential to produce much more meaningful transition pathways than other simulation approaches that try to find pathways in a search space of large numbers of dimensions. In this article, we also propose a new way to define the overlap measure. Past approaches used an inappropriate comparison of the large‐scale conformation displacement against the computed infinitesimal motions of modes. Here, we propose an infinitesimal version of the large‐scale conformation change and then compare it with the modes of motions. As a result, we obtain much better overlap values. Using this new overlap definition, we are also able for the first time to give a clear, intuitive explanation why “open” forms tend to produce better overlap values than “closed” forms with traditional ENMs. Finally, as an application, we present a simple approach to show how domain‐ENM can be used to generated transition pathways for domain‐swapped proteins. Proteins 2006. © 2006 Wiley‐Liss, Inc.

This content is not available in your region!

Continue researching here.

Having issues? You can contact us here