Speaker: Roland Dunbrack (Fox Chase Cancer Center)Â
Title: Structural bioinformatics and AlphaFold modeling of human protein kinases and their interactions
Abstract: Humans have 493 human protein kinase domains with the typical kinase fold, divided into 437 catalytic protein kinases and 56 pseudokinases. We have used structural bioinformatics of substrate-bound kinase structures in the PDB to identify criteria for classifying active and various inactive forms of protein kinases. With AlphaFold2, we have used these criteria to model all 437 catalytic kinases in their active form. By clustering the inactive forms, we have modeled many human kinases in their most likely biologically relevant inactive form. Finally, we have developed new scoring functions within AlphaFold to assess protein-protein interaction models from full-length protein sequences. This function scores interactions well even in the presence of high levels of disorder and accessory (non-interacting) protein domains (github.com/DunbrackLab/IPSAE).