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.