Dynamic architecture of a protein kinase (802.22)

• DOI: 10.1096/fasebj.28.1_supplement.802.22
• Publication Date: 2021-06-15T17:20:36Z
• Authors: Christopher McCle...; Alexandr Kornev; Susan Taylor
• Keywords: Protein kinase domain

To better understand the mechanism of long distance allosteric signaling inside protein kinase core using A (PKA) as a prototype, we obtained 5μs molecular dynamics trajectories in different liganded and conformational states Anton supercomputer, providing for first time an opportunity to observe intermediate-timescale transitions study this stable kinase. We used community analysis identify structurally-contiguous groups residues exhibiting correlated motions catalytic domain. This dynamic partitioning into communities provides framework analyzing local vs. long-range effects mutations, binding, phosphorylation, etc. hypothesize that perturbations will be readily felt within these then propagated possibly lesser extent other elements through motions. Moreover, wealth published mutational data, can annotate with functions. Our functional annotation extremely valuable viewing enzyme terms substructures rather than isolated linear motifs such secondary structure short three or four residue motifs. Figure 1. Functional communitiy map. Each is shown red on PKA. Grant Funding Source: Supported by NIH F32 GM099197, R01 GM19301