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Detection of allosteric signal transmission by information‐theoretic analysis of protein dynamics
Author(s) -
Pandini Alessandro,
Fornili Arianna,
Fraternali Franca,
Kleinjung Jens
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.11-190868
Subject(s) - allosteric regulation , protein dynamics , information transmission , transmission (telecommunications) , signal (programming language) , biological system , function (biology) , computational biology , protein structure , computer science , biophysics , chemistry , biology , biochemistry , telecommunications , microbiology and biotechnology , receptor , computer network , programming language
Allostery offers a highly specific way to modulate protein function. Therefore, understanding this mechanism is of increasing interest for protein science and drug discovery. However, allosteric signal transmission is difficult to detect experimentally and to model because it is often mediated by local structural changes propagating along multiple pathways. To address this, we developed a method to identify communication pathways by an information‐theoretical analysis of molecular dynamics simulations. Signal propagation was described as information exchange through a network of correlated local motions, modeled as transitions between canonical states of protein fragments. The method was used to describe allostery in two‐component regulatory systems. In particular, the transmission from the allosteric site to the signaling surface of the receiver domain NtrC was shown to be mediated by a layer of hub residues. The location of hubs preferentially connected to the allosteric site was found in close agreement with key residues experimentally identified as involved in the signal transmission. The comparison with the networks of the homologues CheY and FixJ highlighted similarities in their dynamics. In particular, we showed that a preorganized network of fragment connections between the allosteric and functional sites exists already in the inactive state of all three proteins.—Pandini, A., Fornili, A., Fraternali, F., Kleinjung, J. Detection of allosteric signal transmission by information‐theoretic analysis of protein dynamics. FASEB J. 26, 868–881 (2012). www.fasebj.org