Molecular Dynamics Simulation of Atypical Kinase ADCK3

Supervisors: Prof. Matteo Dal Peraro

Department of Computational Science and Engineering, EPF, Lausanne


The AarF Domain Containing Kinase 3 (ADCK3) is a member of the ancient UbiB
family within the protein kinase-like (PKL) superfamily. Its importance lies in the fact
that it is a component of the biosynthesis of coenzyme Q (ubiquinone); however, the
actual function of this protein kinase is unknown. Moreover, unlike typical protein
kinases, ADCK3’s N-terminus forms a subdomain above the canonical substrate-binding
pocket which provides possibility for unorthodox kinase function.
To fully understand the link between the protein’s structure and biological func-
tion, we performed molecular dynamics simulations of various ADCK3 constructs: ATP
bound, ADP bound and unbound. The simulations indicate large changes in conforma-
tional motion when the protein kinase is bound to ATP when compared to the apo state
and ADP-bound structure. Using a variety of analysis techniques such as correlation
and PCA, we’ve identi