3RD INTERNATIONAL MEETING : CONFORMATIONAL TRANSITIONS IN MACROMOLECULAR INTERACTIONS
Date:
A wide range of interdisciplinary co-operations between diverse research groups of the GRK was estab-lished (some initiated by the graduates themselves), ena-bling the exchange of scientific expertise and the shared use of equipment. More information about the conference_here More information about the conference here
I presented a poster COMPUTATIONAL ANALYSIS OF CONFORMATIONAL CHANGES IN GSK3-Β/CDK2 KINASES FOR UNDERSTANDING INHIBITOR SELECTIVITY..
ABSTRACT:
GSK3β and CDK2 are highly homologous kinases showing high sequence identity especially in the kinase domain and the ATP‘s binding pocket. This similarity makes the task of developing GSK3β-selective inhibitor challenging. Depending on inhibitors developed in the group of PD Dr. Hilgeroth, computational chemistry methods are applied to get insight in the inhibitor binding, to predict the conformational changes, and to generate predictive models for estimating the binding affinity of novel compounds. The application of the binding free energy method LIE taking into consideration the P-loop flexibility was successful in generating predictive model to explain the varying activity of Fluorene derivatives. Additionally, MD simulation combined with the analysis of trajectories helped to understand the factors that affect the binding affinity. The models can now be applied to further optimize the inhibitor profile.