%0 Journal Article
%T Analysing the origin of long-range interactions in proteins using lattice models
%A Orly Noivirt-Brik
%A Ron Unger
%A Amnon Horovitz
%J BMC Structural Biology
%D 2009
%I BioMed Central
%R 10.1186/1472-6807-9-4
%X Using a computational version of double-mutant cycle analysis, we show that long-range interactions emerge in lattice models even though they are not an input feature of them. The coupling energy of both short- and long-range pairwise interactions is found to become more positive (destabilizing) in a linear fashion with increasing 'contact-frequency', an entropic term that corresponds to the fraction of states in the conformational ensemble of the sequence in which the pair of residues is in contact. A mathematical derivation of the linear dependence of the coupling energy on 'contact-frequency' is provided.Our work shows how 'contact-frequency' should be taken into account in attempts to stabilize proteins by introducing (or stabilizing) contacts in the native state and/or through 'negative design' of non-native contacts.There is a wealth of information that indicates that distant sites in proteins are often coupled to each other energetically. Evidence for such coupling initially emerged through studies of allosteric regulation of proteins [1] when it became clear that allosteric control is often achieved by ligand binding-induced conformational changes that are propagated from one ligand binding site to other distant sites. Later, it became possible to identify distant sites in proteins that are coupled to each other energetically by protein engineering through the use of the double-mutant cycle (DMC) method [for review see ref. [2]]. It has become clear from many such DMC studies that distant sites in proteins are often coupled to each other in a weak but significant manner [for review see ref. [3]]. More recently, it has become possible to demonstrate long-range coupling experimentally also by employing NMR methods [4]. Finally, computational methods have also indicated the presence of long-range communication in proteins. One class of computational methods is based on detection of co-evolving residues in multiple sequence alignment data. Such methods were orig
%U http://www.biomedcentral.com/1472-6807/9/4