MD simulations data for: Role of the αC-β4 loop in protein kinase structure and dynamics

Although the aC-b4 loop is a stable feature of all protein kinases, the
importance of this motif as a conserved element of secondary structure, as
well as its links to the hydrophobic architecture of the kinase core, has
been underappreciated. We first review the motif and then describe how it
is linked to the hydrophobic spine architecture of the kinase core, which
we first discovered using a computational tool, Local Spatial Pattern
(LSP) alignment. Based on NMR predictions that a mutation in this motif
abolishes the synergistic high-affinity binding of ATP and a pseudo
substrate inhibitor, we used LSP to interrogate the F100A mutant. This
comparison highlights the importance of the aC-b4 loop and key residues at
the interface between the N- and C-lobes. In addition, we delved more
deeply into the structure of the apo C-subunit, which lacks ATP. While apo
C-subunit showed no significant changes in backbone dynamics of the aC-b4
loop, we found significant differences in the side chain dynamics of K105.
The LSP analysis suggests disruption of communication between the N- and
C-lobes in the F100A mutant, which would be consistent with the structural
changes predicted by the NMR spectroscopy.