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Proposing Institution

Max-Planck-Institute for biophysical Chemistry
Project Manager

Prof. Dr. Helmut Grubmüller
Am Fassberg 11
37077 Göttingen
Abstract
Due to the recent revolution in cryo electron microscopy (cryo-EM) which allows to determine structures of macromolecular complexes at atomic resolution, cryo-EM has gained popularity in the field of structural biology. To interpret the wealth of cryo-EM data, which is expected to increase tremendously over the coming years, HPC will be crucial. In the proposed project, we aim at developing molecular dynamics (MD) methods to advance the interpretation of cryo-EM data and thus to fully exploit the huge amount of data. Specifically, cryo-EM provides information on structural heterogeneity and ensembles of macromolecules. To obtain cryo-EM images of macromolecules, the samples first have to be rapidly cooled down to liquid nitrogen temperatures. How the cooling procedure perturbs the structural ensemble is currently unknown. To quantify the effects of cooling, in the first part of our proposed project, we will perform cooling simulations of the ribosome starting from a room temperature ensemble. To estimate the cooling effects on the time scales of the experiment, we plan to use a statistical model of the cooling process with parameters obtained from the simulations. Further, with the huge increase of available high quality cryo-EM data, refinement of atomic models is becoming a bottleneck. In the second part of the project, we will develop an automated MD based protocol for refinement and model validation specifically for high-resolution cryo-EM maps.The results will allow us to advance the interpretation of structural data obtained by cryo-EM using HPC and to improve our understanding of the physics underlying the cryo-EM experiments.

Impressum, Conny Wendler