Publication:
Protein-protein interactions: organization, cooperativity and mapping in a bottom-up Systems Biology approach

dc.contributor.coauthorMa, BY
dc.contributor.coauthorRogale, K
dc.contributor.coauthorGunasekaran, K
dc.contributor.coauthorNussinov, R
dc.contributor.departmentDepartment of Chemical and Biological Engineering
dc.contributor.departmentCCBB (The Center for Computational Biology and Bioinformatics)
dc.contributor.kuauthorKeskin, Özlem
dc.contributor.schoolcollegeinstituteCollege of Engineering
dc.contributor.schoolcollegeinstituteResearch Center
dc.date.accessioned2024-11-09T23:09:30Z
dc.date.issued2005
dc.description.abstractUnderstanding and ultimately predicting protein associations is immensely important for functional genomics and drug design. Here, we propose that binding sites have preferred organizations. First, the hot spots cluster within densely packed 'hot regions'. Within these regions, they form networks of interactions. Thus, hot spots located within a hot region contribute cooperatively to the stability of the complex. However, the contributions of separate, independent hot regions are additive. Moreover, hot spots are often already pre-organized in the unbound (free) protein states. Describing a binding site through independent local hot regions has implications for binding site definition, design and parametrization for prediction. The compactness and cooperativity emphasize the similarity between binding and folding. This proposition is grounded in computation and experiment. It explains why summation of the interactions may over-estimate the stability of the complex. Furthermore, statistically, charge-charge coupling of the hot spots is disfavored. However, since within the highly packed regions the solvent is screened, the electrostatic contributions are strengthened. Thus, we propose a new description of protein binding sites: a site consists of (one or a few) self-contained cooperative regions. Since the residue hot spots are those conserved by evolution, proteins binding multiple partners at the same sites are expected to use all or some combination of these regions.
dc.description.indexedbyWOS
dc.description.indexedbyScopus
dc.description.indexedbyPubMed
dc.description.issue2
dc.description.openaccessYES
dc.description.publisherscopeInternational
dc.description.sponsoredbyTubitakEuN/A
dc.description.sponsorshipNCI NIH HHS [N01-CO-12400] Funding Source: Medline
dc.description.sponsorshipNATIONAL CANCER INSTITUTE [Z01BC010441] Funding Source: NIH RePORTER
dc.description.volume2
dc.identifier.doi10.1088/1478-3975/2/2/S03
dc.identifier.eissn1478-3975
dc.identifier.issn1478-3967
dc.identifier.quartileQ3
dc.identifier.scopus2-s2.0-22244465254
dc.identifier.urihttps://doi.org/10.1088/1478-3975/2/2/S03
dc.identifier.urihttps://hdl.handle.net/20.500.14288/9315
dc.identifier.wos234992400004
dc.keywordsStructurally conserved residues
dc.keywordsEnergy hot-spots
dc.keywordsInteraction sites
dc.keywordsInteraction network
dc.language.isoeng
dc.publisherInstitute of Physics (IOP) Publishing
dc.relation.ispartofPhysical Biology
dc.subjectBiochemistry
dc.subjectMolecular biology
dc.subjectBiophysics
dc.titleProtein-protein interactions: organization, cooperativity and mapping in a bottom-up Systems Biology approach
dc.typeReview
dspace.entity.typePublication
local.contributor.kuauthorKeskin, Özlem
local.publication.orgunit1College of Engineering
local.publication.orgunit1Research Center
local.publication.orgunit2Department of Chemical and Biological Engineering
local.publication.orgunit2CCBB (The Center for Computational Biology and Bioinformatics)
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