Analysis of Biomolecular and Cellular Systems

Topics

• Introduction, goals and rationale for the course, protein-ligand interactions
• Experimental techniques: Titration analysis, fractional saturation, the “pseudo-first order approximation” (PFOA), isothermal titration calorimetry (ITC), mass spectrometry (MS)
• Co-immunoprecipitation (Co-IP) and mass spectrometry (MS), Fӧrster resonance energy transfer (FRET), primary ligation assay (PLA), surface plasmon resonance (SPR)
• Enzyme kinetics, Michaelis-Menten kinetics
• Kinase engineering, competitive inhibition, non-competitive inhibition, epidermal growth factor receptor (EGFR) in cancer, regulation of kinase activity
• Constitutive kinases, modeling kinases, how to shut down kinases, multiple substrates, modeling abstraction, mitogen-activated protein kinase (MAPK) cascade
• Ultrasensitivity / amplification in the MAPK cascade
• Signal shut-down
• Ligand depletion
• Transcription factor (TF) phosphorylation
• Transcriptional regulation: Simple regulation, negative autoregulation, positive autoregulation
• Predictive models of biology, genome editing, sensors, light-activated proteins, new enzymes, electrostatics
• Hydrogen bonding, the hydrophobic effect, how we represent proteins
• Paralogues and orthologues, protein therapeutics
• Specificity
• The metropolis algorithm
• Gradient descent, molecular dynamics, ΔΔG for small molecules, pharma priorities
• Drug development case study: Imatinib
• Guest lecture by Rebecca L. Carrier. Impact of drug delivery of effectiveness
• Protein folding: Thermodynamics
• Kinetics of folding, predicting protein structure
• Structure from sequence
• Kinases, graph theory, experimental and computational techniques