cavalli mondayseminar 2016.docx - biozentrum.unibas.ch filebasel computational biology seminar...
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BaselComputationalBiologySeminar
AndreaCavalliInstituteforresearchinBiomedicine
Bellinzona,Switzerland
Modelingdynamics
Proteinsaremoleculesinvolvedinessentiallyallthecomplexbiochemicalreactionsthattakeplacein
living organisms. In order to perform their functions they undergo conformational fluctuations on
timescales ranging from nanoseconds to milliseconds and beyond. It is, therefore, important to
developmethodscapableofcharacterizingthesemotions.
Nuclear magnetic resonance (NMR) spectroscopy and small-angle x-ray spectroscopy (SAXS) are
powerful techniques thatenables thedeterminationof the structuresanddynamicsofproteinsat
atomic resolution. Since measurements produce values of observables resulting from time and
ensembleaverages,theirinterpretationisfacilitatedbyconsideringensemblesofstructures.
The determination of an ensemble of conformations from experimental information about just
averagevaluesseemstobeanill-definedproblem.InthetalkIwillshowthatbyusingthePrinciple
of Maximum Entropy (PME) it is possible to chose a special distribution (i.e., an ensemble of
structures)amongall thosethatareconsistentwiththeexperimentally-determinedaveragevalues
byimposingtheaveragevaluesthemselvesasthermodynamicconstraints.Thisparticularmaximum
entropydistributionprovidesanaccuraterepresentationoftheunknownBoltzmanndistributionof
thesystem.
Theproblemofdeterminingstructuralensemblescanthusbesolvedunambiguouslywithoutmaking
any additional assumption apart from the requirement that the experimental data should be
consistentwithitinthesenseofthemaximumentropyprinciple.
Furthermore, Iwill show, that to implement themaximum entropy principle in a computationally
efficient manner, it is possible to use experimental measurements as replica-averaged structural
restraintsinmoleculardynamicssimulations.
Date: Monday,November21th,2014
Time: 16:00h
Room: Lounge(level13),Klingelbergstrasse61(vis-à-vis Pharmazentrum)
Contact:OlivierBignucolo([email protected])