Project 11730 (GPU, Core21) to FAH

[rafwiewiora]

Project 11730 now on FAH!

Stats:

11730:
# atoms: 68613
credit: 8464
k-factor: 0.75
timeout: 7d
deadline: 10d
precision: mixed

We are running follow-up simulations for this awesome paper: https://www.biorxiv.org/content/early/2018/05/25/331637

"Protein kinases are crucial to coordinate cellular decisions and therefore their activities are
strictly regulated. We used ancestral resurrection to uncover a mechanism underlying the
evolution of kinase control within the ERK family of Mitogen Activated Protein Kinases (MAPKs).
Kinase activities switched from high to low intrinsic autophosphorylation at the transition from
the ancestors of ERKs1-5 and ERKs1-2. A shortening of the loop between b3-aC and a mutation in
the gatekeeper residue drove this transition. Molecular dynamics simulations suggested that the
change in the b3-aC loop length affected kinase cis-autophosphorylation by altering the
positioning of catalytic residues and by allowing greater flexibility in the L16 kinase loop. This
latter effect likely synergizes with the known role of gatekeeper mutations in facilitating domain
closure and thus kinase activation, providing a rationale for the synergy between the two
evolutionary mutations. Our results shed light on the evolutionary mechanisms that led to tight
regulation of a central kinase in development and disease."

Thanks folks!