Inquiry Immersion 2023 - DRUG DESIGN: Personal Genome Interpretation in the post-AlphaFold world

INSTRUCTORS

• James Fraser (Lead Instructor)

LOCATION

Varies day by day (see schedule)! How exciting…

OVERVIEW

Alphafold is one of the buzziest breakthroughs of recent years. What does it mean to predict a structure of a protein and how is that useful for: 1) designing new drugs and 2) interpreting genomes?

MINI COURSE OBJECTIVES

• Identify an urgent and significant gap in medical knowledge and/or practice.
• Propose rationale and novel strategies to address that gap in medical knowledge and/or practice using tools and techniques germane to the relevant Domain(s) of Science.
• Engage with researchers working on the topic explored and collaborate on potential scholarly research.

TOPIC OBJECTIVES

• Employ visualization software to examine alphafold models
• Model mutations in protein stuctures
• Examine the interactions between proteins and small molecules

MINI COURSE DEI Focus

• The role of “who owns” genomes will be discussed.

Schedule

Tuesday Jan 10 - 3:00-4:45PM - Byers Hall 212

• JF overview of the class
  • what is a protein (a membrane protein)
  • forces governing protein folding, levinthal paradox, structure/folding prediction
  • forces governing ligand/drug binding
  • intro to GPCRs, importance of struture prediction in GPCRs, importance of state prediction in GPCRs
  • MPRA/MAVE/DMS - Structural and functional characterization of G protein–coupled receptors with deep mutational scanning
  • Pharmacogenomics of GPCR Drug Targets
• Install ChimeraX before next class link

Wednesday Jan 11 - 3:00-4:45PM - Mission Hall 2105

• Tanja Kortemme
  • what is AlphaFold really and other trends in protein structure prediction and design

Thursday Jan 12 - 3:00-4:45PM - Mission Hall 2105

• Moez Dawood - over zoom!
• who owns genomes?
  • Establishing a blockchain-enabled Indigenous data sovereignty framework for genomic data
  • The Illusion of Inclusion — The “All of Us” Research Program and Indigenous Peoples’ DNA
  • Accounting for diversity in the design of CRISPR-based therapeutic genome editing

Friday Jan 13 - 3:00-4:45PM - Mission Hall 2105

• Tony Capra
  • The 3D mutational constraint on amino acid sites in the human proteome
  • Personalized structural biology reveals the molecular mechanisms underlying heterogeneous epileptic phenotypes caused by de novo KCNC2 variants

Tuesday Jan 17 - 3:00-4:45PM - Byers Hall 209

• Tom Goddard: ChimeraX demo
  • Elucidating the active delta-opioid receptor crystal structure with peptide and small-molecule agonists.
  • VR links:
    • Opiod
    • Coronavirus

Wednesday Jan 18 - 3:00-4:45PM - Mission Hall 2105

• Gabriella Estevam and JF
  • DMS and personalized medicine
  • PDB 2WGJ - crizotinib
  • PDB 3DKC - ATP
    • Y1230E
    • G1163F
    • I1084G
    • M1211E
    • D1228L
    • Y1093K