Protein Dynamics under Non-Ambient Conditions

Supervisors: Dr. Alke Meents (DESY), Prof. Matthias Rarey (UHH)

Protein flexibility plays a pivotal role in enzymatic activities, their regulation, the binding of native ligands and drugs, and further bio-molecular processes. Therefore, the investigation of protein dynamics is a prerequisite for understanding protein function and dysfunction which is often connected to diseases. Usually, our knowledge of protein structures is restricted to static snapshots and does not allow for an experimental in-depth analysis of  flexibility. However, time-resolved X-ray crystallography enables investigations of proteins in motion. The development of the temperature-jump methodology using an infrared-laser to increase the temperature of the proteins within ns enables the subsequent analysis of the protein structure at the atomic level at different time intervals.
The obtained data offers a unique means to discover dynamic networks in proteins and establish a better understanding of the evolution of motions in proteins. The resulting atomic models and descriptors of protein flexibility can be compared to and supplemented by molecular dynamics simulation data, also shedding light on the correlations between both methods. The interplay between this in silico method and the experimental data can subsequently be employed to analyze the impact of various perturbations on protein behavior, enable predictions of protein dynamics and establish generic models of protein flexibility