?url_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Adc&rft.relation=http%3A%2F%2Fd-scholarship-dev.library.pitt.edu%2F7610%2F&rft.title=COARSE-GRAINED+TECHNIQUES+TO+STUDY+DYNAMICS+OF+LONG-TIME+SCALE+CONFORMATIONAL+CHANGES+OF+PROTEINS&rft.creator=Essiz+Gokhan%2C+Sebnem&rft.description=The+Rotation+and+Translation+block+(RTB)+method+of+Durand+et+al.+%5BBiopolymers+34%2C+759+(1994)%5D+and+Tama+et+al.+%5BProteins+41%2C+1+(2000)%5D%2C+which+is+an+appealing+way+to+calculate+low+frequency+normal+modes+of+biomolecules+by+restricting+the+space+of+motions+to+exclude+internal+motions+of+pre-selected+rigid+fragments+within+the+molecule%2C+is+extended+to+a+method+for+computing+the+Newtonian+dynamics+of+a+biomolecule%2C+or+any+large+molecule%2C+with+effective+rigid-body+constraints+applied+to+a+pre-chosen+set+of+internal+molecular+fragments.+This+method%2C+to+be+termed+RTB-dynamics+does+not+require+the+construction+of+the+matrix+of+second+spatial+derivatives+of+the+potential+energy+function%2C+and+can+be+used+to+compute+the+classical+dynamics+of+a+system+moving+in+an+arbitrary+anharmonic+force+field+with+an+efficient+way+of+freezing+out+the+high+frequency+motions+within+rigid+fragments.+Moreover%2C+an+approximation+scheme+is+developed+to+compute+Brownian+motion+according+to+the+Langevin+Equation+for+a+molecular+system+moving+in+a+harmonic+force+field+and+characterized+by+one+or+more+rigid+internal+fragments+by+using+the+RTB+methodology.+To+illustrate+these+methods+elementary+numerical+applications+to+signal+propagation+in+the+small+membrane-bound+polypeptide+gramicidin-A+are+presented.+Finally%2C+Dynamic+Linear+Response+Theory+(DLRT)+is+adapted+to+the+problem+of+computing+the+time+evolution+of+the+atomic+coordinates+of+a+protein+in+response+to+the+unbinding+of+a+ligand+molecule+from+a+binding+pocket+within+the+protein.+DLRT+relates+the+non-equilibrium+motion+of+the+protein+atoms+which+ensues+after+the+ligand+molecule+dissociates+to+equilibrium+dynamics+in+the+force+field%2C+or+equivalently%2C+on+the+potential+energy+surface+(PES)+relevant+to+the+unliganded+protein.+We+numerically+illustrate+the+application+of+DLRT+for+a+simple+harmonic+oscillator+model+of+the+ferric+binding+protein%2C+and+for+an+analogous+model+of+T4+lysozyme+including+the+solvent+effects+on+the+motion+using+the+Langevin+prescription.+Using+a+physically+appropriate+value+of+the+viscosity+of+water+to+guide+the+choice+of+friction+parameters%2C+we+find+relaxation+time+scales+of+residue-residue+distances+on+the+order+of+several+hundred+ps.+Comparison+is+made+to+relevant+experimental+measurements.&rft.date=2009-06-15&rft.type=University+of+Pittsburgh+ETD&rft.type=PeerReviewed&rft.format=application%2Fpdf&rft.language=en&rft.identifier=http%3A%2F%2Fd-scholarship-dev.library.pitt.edu%2F7610%2F1%2FEssiz_Gokhan_Sebnem_0409_rev.pdf&rft.identifier=++Essiz+Gokhan%2C+Sebnem++(2009)+COARSE-GRAINED+TECHNIQUES+TO+STUDY+DYNAMICS+OF+LONG-TIME+SCALE+CONFORMATIONAL+CHANGES+OF+PROTEINS.++Doctoral+Dissertation%2C+University+of+Pittsburgh.++++(Unpublished)++