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DESCRIPTION:This webinar is by the ELIXIR 3D-BioInfo Community. \n\n				I
 t will be chaired by Dr Neeladri Sen of University College London\n			\n		
 	\n		\n	\n\n\nModeling all 437 catalytic typical protein kinases in the hu
 man proteome in active form\n\nProf. Roland Dunbrack\n	Institute for Cance
 r Research\, Fox Chase Cancer Center\n\nHumans have 437 catalytically comp
 etent protein kinase domains with the typical kinase fold\, similar to PKA
 . From bioinformatics analysis of structures of 40 unique ATP+substrate-bo
 und kinases\, we derived criteria for the active form of protein kinases 
 including the conformation of the DFG motif (in dihedral angles) and the N
 -terminal domain salt bridge\, required for binding ATP and magnesium. Th
 ere are also novel requirements on the position of the N and C terminal p
 ortions of the activation loop\, which lead to the formation of a substrat
 e binding cleft. With these criteria\, only 130 of 437 kinase domains (30
 %) are present in the PDB in complete active\n	form. We used extensive sam
 pling with AlphaFold2 with these active-state structures as templates and 
 shallow multiple sequence alignments of orthologues to make active-conform
 ation models of all 437 human kinases. We show that the pLDDT of the activ
 ation loop is correlated with low model RMSD to the 130 benchmark PDB stru
 ctures. Models of all 437\n	human kinases in the active form are available
  at http://dunbrack.fccc.edu/kincore/active.\n	They are suitable for inte
 rpreting mutations leading to constitutive catalytic activity in cancer as
 \n	well as for templates for modeling substrate-kinase complexes and inhib
 itors which bind to the\n	active state.\n\nThe topological properties of t
 he protein universe\n\nProf. Michael Stumpf\n	The University of Melbourne\
 , Australia\n\nDeep learning methods have revolutionised our ability to pr
 edict protein structures\, allowing us a glimpse into the entire protein u
 niverse. As a result\, our understanding of how protein structure drives f
 unction is now lagging behind our ability to determine and predict protein
  structure. Here\, we describe how topology\, the branch of mathematics co
 ncerned with qualitative properties of spatial structures\, provides a len
 s through which we can identify fundamental organising features across the
  known protein universe. We identify topological determinants that capture
  global features of the protein universe\, such as domain architecture and
  binding sites. Additionally\, our analysis also identified highly specifi
 c properties\, so-called topological generators\, that can be used to prov
 ide deeper insights into protein structure-function and evolutionary relat
 ionships. We used our approach to determine structural\, functional and di
 sease consequences of mutations\, explain differences in properties of pro
 teins in mesophiles and thermophiles\, and the likely structural and funct
 ional consequences of polymorphisms in a protein. Overall\, we present a p
 ractical methodology for mapping the topology of the known protein univers
 e at scale\n\nYou can find previous webinars from the 3D-BioInfo Community
  on the Community webinars page.\n\n 
SUMMARY:Latest Developments in Structural Bioinformatics
URL;VALUE=URI:https://www.elixir-europe.org/events/latest-developments-stru
 ctural-bioinformatics
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