Signal Propagation in Proteins and Relation to Equilibrium Fluctuations 英文参考文献.docVIP

SignalPropagationinProteinsandRelation toEquilibriumFluctuations Chakra Chennubhotla, Ivet Bahar* DepartmentofComputationalBiology,SchoolofMedicine,UniversityofPittsburgh,Pittsburgh,Pennsylvania,UnitedStatesofAmerica Elastic network (EN) models have been widely used in recent years for describing protein dynamics, based on the premise that the motions naturally accessible to native structures are relevant to biological function. We posit that equilibriummotionsalsodeterminecommunicationmechanismsinherenttothenetworkarchitecture.Tothisend,we explorethestochasticsofadiscrete-time,discrete-stateMarkovprocessofinformationtransferacrossthenetworkof residues.Wemeasurethecommunicationabilitiesofresiduepairsintermsofhitandcommutetimes,i.e.,thenumber ofstepsittakesonanaveragetosendandreceivesignals.Functionallyactiveresiduesarefoundtopossessenhanced communicationpropensities,evidencedbytheirshorthittimes.Furthermore,secondarystructuralelementsemerge as efficient mediators of communication. The present findings provide us with insights on the topological basis of communication in proteins and design principles for efficient signal transduction. While hit/commute times are information-theoreticconcepts,acentralcontributionofthisworkistorigorouslyshowthattheyhavephysicalorigins directlyrelevanttotheequilibriumfluctuationsofresiduespredictedbyENmodels. Citation: Chennubhotla C, Bahar I (2007) Signal propagation in proteins and relation to equilibrium fluctuations. PLoS Comput Biol 3(9): e172. doi:10.1371/journal.pcbi. 0030172 the Kirchhoff matrix of inter-residue contacts that underlie theGNMmethodology.Additionally,wepresentnewinsights Introduction Proteinsfunctionneitherasstaticentitiesnorinisolation, under physiological conditions. They are instead subject to constantmotionsandinteractions,bothwithinandbetween molecules.Thesemotionscanbeeitherrandom?uctuations orconcertedfunctionalchangesinconformations;andtheir sizescanvaryfromlocalizedmotions(e.g.,singleaminoacid sidechai