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Bernal Institute Research Forum

Tue, 08 Aug 2017

Date: Tuesday, August 8, 2017
Time: 11:00 to 12:00
Duration: One hour
Contact: Joan O'Riordan -
Location: MSG-025 MSSI Building Extension, Ireland

Dr Nuria Plattner, The Free University of Berlin, Germany.

Protein Binding Kinetics Revealed in Atomic Detail Using High-throughput Molecular Dynamics and Markov Modelling

Markov modelling in combination with high-throughput molecular dynamics (MD) simulations allows to overcome the parallelization limit and resolve the kinetics of complex systems in atomic detail. The method has been used successfully to build models of protein-ligand interactions for the serine protease Trypsin and its competitive inhibitor Benzamidine, as well as to describe detailed interactions of the ribonuclease Barnase and its inhibitor Barstar. Markov state modelling summarizes the complex kinetics of protein-ligand binding and protein-protein interactions in multi-state models which can then be used to predict functionally relevant observables of these systems over long timescales. For Trypsin/Benzamidine the interplay between different protein conformations and ligand binding has been assessed, providing direct evidence of conformational plasticity in Trypsin-like serine proteases. For Barnase/Barstar, protein-protein association and dissociation has been resolved in full atomic detail. The proteins initially associate into a structurally diverse set of non-native encounter states, which are eventually funnelled into intermediate transition states in which Barnase and Barstar are flexibly associated by a few key amino acids. Reaching the final bound configuration requires tens of microseconds after the initial encounter. The bound state fluctuates on the microseconds timescale, between a more stable substate and a less tightly bound and flexible substate. The complex remains stable for minutes, and exhibits multiple geminate rebinding events through non-native intermediates prior to dissociating.

Dr Plattner completed her PhD in Physical Chemistry in 2009 at the University of Basel, Switzerland. Since 2012, she is a research associate with the Computational Molecular Biology group at the Free University of Berlin, Germany. Prior to this, she was a postdoctoral researcher at the University of Basel and also at Brown University, Providence, USA. Current projects as principal investigator include SFB TRR 186 “Molecular Switches”, a transregional collaborative research network funded by the German Research Foundation (DFG) and Research Unit “Dynion”, focusing on the dynamics of ion channels, a collaborative research unit funded by DFG. Awards/fellowships include 2013 Lise-Meitner Fellowship of the Austrian FWF (2 years postdoctoral funding, declined); 2012 International postdoctoral research fellowship from the Einstein Foundation, Berlin, (5 years postdoctoral funding); 2012 Fellowship for advanced researchers from the Swiss National Science Foundation (2 years postdoctoral funding, declined); 2010 Fellowship for prospective researchers from the Swiss National Science Foundation (1 year postdoctoral funding used at Brown University).

Tea/coffee will be available at 10h45

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