Cavalli MondaySeminar 2016.docx - biozentrum.unibas.ch fileBasel Computational Biology Seminar...
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Basel Computational Biology Seminar Andrea Cavalli Institute for research in Biomedicine Bellinzona, Switzerland Modeling dynamics Proteins are molecules involved in essentially all the complex biochemical reactions that take place in 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 develop methods capable of characterizing these motions. Nuclear magnetic resonance (NMR) spectroscopy and small-angle x-ray spectroscopy (SAXS) are powerful techniques that enables the determination of the structures and dynamics of proteins at atomic resolution. Since measurements produce values of observables resulting from time and ensemble averages, their interpretation is facilitated by considering ensembles of structures. The determination of an ensemble of conformations from experimental information about just average values seems to be an ill-defined problem. In the talk I will show that by using the Principle of Maximum Entropy (PME) it is possible to chose a special distribution (i.e., an ensemble of structures) among all those that are consistent with the experimentally-determined average values by imposing the average values themselves as thermodynamic constraints. This particular maximum entropy distribution provides an accurate representation of the unknown Boltzmann distribution of the system. The problem of determining structural ensembles can thus be solved unambiguously without making any additional assumption apart from the requirement that the experimental data should be consistent with it in the sense of the maximum entropy principle. Furthermore, I will show, that to implement the maximum entropy principle in a computationally efficient manner, it is possible to use experimental measurements as replica-averaged structural restraints in molecular dynamics simulations. Date: Monday, November 21 th , 2014 Time: 16:00 h Room: Lounge (level 13), Klingelbergstrasse 61 (vis-à-vis Pharmazentrum) Contact: Olivier Bignucolo ([email protected])
Transcript of Cavalli MondaySeminar 2016.docx - biozentrum.unibas.ch fileBasel Computational Biology Seminar...
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])
