Conformational Ensembles from Experimental Data and Computer Simulations

Conformational Ensembles from Experimental Data and Computer Simulations

Poster Abstracts

55-POS Board 15 Coupling Nuclear Magnetic Resonance and Molecular Dynamics Simulations to Study Protein Dynamics Micha Kunze , Kresten Lindorff-Larsen. University of Copenhagen, Copenhagen, Denmark. Symbiotic use of high-resolution ensemble measurements such as NMR and molecular dynamics (MD) simulations is crucial for an in-depth understanding and visualization of a proteins structural ensemble. My presentation focuses on applications where we use experiment and simulation in tandem to understand the structure-dynamics-function relationship of different proteins. We use experimental data to restrain and correct MD simulations, e.g. chemical shift or NOE data [1,2]. In this way we can gain insight into the mechanism of allosteric enzyme regulation [1] or the structural ensemble of peptides [2]. Vice versa we use simulations to guide experiments, by e.g. suggesting mutations to alter enzymatic activity [3] or by suggesting specific experiments to probe conformational changes observed in simulations. References: [1] Choy MS, Li Y, Machado L, Kunze MBA, Connors CR, X W, Lindorff-Larsen K, Page R & Peti W (2017) Conformational Rigidity and Protein Dynamics at Distinct Timescales Regulate PTP1B Activity and Allostery. Molecular Cell 65, 644–658. [2] Tran PT, Larsen CØ, Røndbjerg T, De Foresta M, Kunze MBA, Marek A, Løper JH, Boyhus L-E, Knuhtsen A, Lindorff-Larsen K & Pedersen DS (2017) Diversity-Oriented Peptide Stapling: A Third Generation Copper-Catalysed Azide-Alkyne Cycloaddition Stapling and Functionalisation Strategy. Chem. Eur. J. 23, 3490–3495. [3] Kunze MBA, Wright DW, Werbeck ND, Kirkpatrick J, Coveney PV & Hansen DF (2013) Loop Interactions and Dynamics Tune the Enzymatic Activity of the Human Histone Deacetylase 8. J. Am. Chem. Soc. 135, 17862–17868.

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