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Biophysics of Macromolecules – Lecture Notes

Literature

  • Phillips, Kondev and Theriot "Physical Biology of the Cell"
  • Jonathon Howard "Mechanics of Motor Proteins and the Cytoskeleton"
  • Sackmann and Merkel "Lehrbuch der Biophysik" (in German) [http://www.biophy.de/]
  • Alberts et al. "Molecular Biology of the Cell"
  • Nelson "Biological Physics"

Reader for the class ("Skript")

Schedule and Lecture notes "Biophysics of Macromolecules

  • If you need the password for the files, ask me in class or send me an email.
  • Recordings of the lectures are available on LMUcast. Go to the "Recording" tab above and follow the link. You need an LMU account to access  the recordings.


Tuesday, April 13
  • Course introduction and overview
  • Fundamentals of molecular biology: Life, cells, evolution
  • Lecture slides [PDF, with password]


Thursday, April 15
  • Cells and model organisms
  • The central dogma of molecular biology
  • Introduction to biological macromolecules: DNA, RNA, and proteins
  • Lecture slides [PDF, with password]


Tuesday, April 20
  • Protein Data Bank (PDB)
  • Physical interactions of biological macromolecules
  • Molecular dynamics simulations
  • Comparison: MD vs. quantum simulations
  • Lecture slides [PDF, with password]


Thursday, April 22
  • Protein folding: Secondary structure, Ramachandran plots, Structural motifs
  • Anfinsen's hypothesis, Levinthal's paradox, Dill's folding funnel
  • Discussion of PS1
  • Lecture slides [PDF, with password]


Tuesday, April 27
  • Protein-ligand interactions
  • Binding equilibrium
  • Cooperativity and allostery: Hill model, MWC model, KNF model
  • Inverted classroom" assignment:
    - Watch David Baker explain the potential of proteins design
    [link]
    - Watch Susan Lindquist explain protein misfolding diseases [link]
    We will dicuss protein design and protein misfolding disease next Thursday.
  • Lecture slides [PDF, with password]


Thursday, April 29
  • Protein-ligand interactions and cooperativity, cont.
  • Derivation of the shift in equilibrium in the MWC model
  • Discussion of PS2
  • Lecture slides [PDF, with password]


Tuesday, May 4
  • Selected topics protein folding: Chaperones, proline isomerization, disulfide bonds
  • Protein design
  • Misfolding diseases
  • Lecture slides [PDF, with password]


Thursday, May 6
  • Traditional roles of RNA: mRNA, tRNA, rRNA
  • RNA "beyond the central dogma": Ribozymes, RNA interference, ribowitches
  • "Inverted classroom" assignment: Watch Jennifer Doudna explain CRISPR/Cas [link]
    We will dicuss CRISPR/Cas and the video next Tuesday.
  • Discussion of PS3
  • Lecture slides [PDF, with password]


Tuesday, May 11
  • CRISPR/Cas: a batecterial defense system turned powerful gene editing tool
  • The RNA folding problem and the importance of electrostatics
  • Nucleic acid-ion interactions
  • Lecture slides [PDF, with password]



Thursday, May 13

Ascencion Day ("Himmelfahrt") - No class


Tuesday, May 18
  • Recap: Nucleic acid-ion interactions and the ion atmosphere
  • Small-angle X-ray scattering
  • Poisson-Boltzmann theory: introduction and solution for infinite plane
  • Poisson-Boltzmann for complex nucleic acids
  • Lecture slides [PDF, with password]


Thursday, May 20
  • Recap: Poisson-Boltzmann
  • Comparison: experimental data and Poisson-Boltzmann predictions
  • MD simulations for nucleic acid-ion interactions
  • Discussion of PS4
  • Introduction to single-molecule force manipulation techniques
  • Lecture slides [PDF, with password]



Tuesday, May 25

Pentecost ("Pfingsten") - No class


Thursday, May 27
  • Viruses: Basics, Baltimore classification, origin
  • Case study: SARS-CoV-2
  • Lecture slides [PDF, with password]


Tuesday, June 1
  • Single-molecule force spectroscopy techniques
  • Isotropic elastic rod (Kirchhoff rod) model
  • Freely-joined chain and worm-like chain
  • Freely-jointed chain: root mean end-to-end distance
  • Freely-jointed chain under external force
  • Lecture slides [PDF, with password]


Thursday, June 3
Feast of Corpus Christi ("Fronleichnam") - No class


Tuesday, June 8
  • Stretching DNA: Entropic stretching modeled as a FJC and WLC
  • Enthalpic stretching and the stretch modulus; overstretching
  • Stretching proteins: AFM force spectroscopy on titin Ig domains
  • Magnetic tweezers: Instrumentation and force-calibration
  • Twisting DNA with magnetic tweezers
  • Lecture slides [PDF, with password]


Thursday, June 10
  • Recap: Twisting DNA
  • Magnetic torque tweezers and single-molecule measurements
  • DNA bending and twisting stiffness
  • Discussion of PS5
  • Lecture slides [PDF, with password]


Tuesday, June 15
  • Radius of gyration and end-to-end distance for FJC
  • Self-avoidance and the Flory exponent
  • Experimental evidence for self-avoidance: SAXS measurements for unfolded proteins and nucleic acids
  • Fluorescence measurements for DNA in 2D
  • Lecture slides [PDF, with password]


Thursday, June 17
  • AFM imaging
  • Force sensing and imaging modes
  • Sample preparation and resolution
  • AFM imaging applications: intrinscally disordered proteins, long DNA, and nucleosome conformations
  • Lecture slides [PDF, with password]



Tuesday, June 22
  • Guest lecture Prof. Thorben Cordes (Department of Biology, LMU Munich)
  • Förster Resonance Energy Transfer (FRET)
  • Coformational dynamics of proteins
  • Lecture slides [PDF, with password]



Thursday, June 24
  • Potential topics for TED talks
  • Pointers on giving scientific presentations
  • Energy in biological systems
  • Enzyme-catalyzed reactions in biological systems
  • Michaelis-Menten theory of enzymatic reactions
  • Lecture slides [PDF, with password]


Tuesday, June 29
  • Michaelis-Menten theory of enzymatic reactions
  • Michaelis-Menten: kcat/Km regime, point of half-maximal rate, saturation regime
  • Lecture slides [PDF, with password]

     


Thursday, July 1
  • Guest lecture Prof. Claudia Veigel (Medical school, LMU Munich)
  • Optical tweezers
  • Molecular motors and the cytoskeleton
  • Mechano-chemical coupling of myosin motors
  • Lecture slides [PDF, with password]


Lab tour, July 2
  • Your chance to see magnetic tweezers, AFMs, our wetlab, etc. in real life.
  • We will meet at 13:30 in the seminar room on the first floor of Amalienstrasse 54. Here is how to find us: [link].
  • Please wear a FFP2 mask in the building.



Tuesday, July 6
  • Diffusion limited enzymes
  • Super-diffusive enzymes
  • Michaelis-Menten at the single-molecule level
  • Discussion PS7
  • Life at low Reynolds number
  • Lecture slides [PDF, with password]


Tuesday, July 8
  • Student presentations "Biophysics TED Talks" - PART 1
  • Schedule [PDF]


Thursday, July 13
  • Student presentations "Biophysics TED Talks" - PART 2
  • Schedule [PDF]


Tuesday, July 15
  • Student presentation back-up date
  • Presentation of possible master thesis projects
  • Question & Answer session / exam preparation
  • Lecture slides [PDF, with password]


FINAL EXAMS: Oral exams; dates to be announced