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(olivier.bignucolo@unibas.ch)