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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. It is the same password as for the Zoom meetings.
  • 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 21
  • Course introduction and overview
  • Fundamentals of molecular biology: Life, cells, evolution
  • Lecture slides [PDF, with password]


Thursday, April 23
  • 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 28
  • Protein Data Bank (PDB)
  • Physical interactions of biological macromolecules
  • Molecular dynamics simulations
  • Comparison: MD vs. quantum simulations
  • Lecture slides [PDF, with password]


Thursday, April 30
  • Protein folding: Secondary structure, Ramachandran plots, Structural motifs
  • Anfinsen's hypothesis, Levinthal's paradox, Dill's folding funnel
  • Lecture slides [PDF, with password]


Tuesday, May 05
  • Protein-ligand interactions
  • Binding equilibrium
  • Cooperativity and allostery: Hill model, MWC model, KNF model
  • Lecture slides [PDF, with password]


Thursday, May 07
  • Protein-ligand interactions and cooperativity, cont.
  • Derivation of the shift in equilibrium in the MWC model
  • Selected topic protein folding: circular dichroisim, disulfide bridges, proline isomerization
  • Lecture slides [PDF, with password]


Tuesday, May 12
  • Traditional roles of RNA: mRNA, tRNA, rRNA
  • RNA "beyond the central dogma": Ribozymes, RNA interference, ribowitches
  • The RNA folding problem and the importance of electrostatics
  • "Inverted classroom" assignment: Watch Jennifer Doudna explain CRISPR/Cas [link]
    We will dicuss CRISPR/Cas and the video next Thursday.
  • Lecture slides [PDF, with password]


Thursday, May 14
  • CRISPR/Cas: a batecterial defense system turned powerful gene editing tool
  • Nucleic acid-ion interactions
  • Small-angle X-ray scattering (SAXS)
  • Lecture slides [PDF, with password]


Tuesday, May 19
  • Nucleic acid-ion interactions, cont.
  • Poisson-Boltzmann theory and PB equation
  • Derivation Poisson-Boltzmann for infinite plane
  • Introduction to viruses
  • "Inverted classroom" assignment: Watch Britt Glaunsinger explain Coronaviruses [link]
    - We will discuss Coronaviruses next Thursday in class.
    - Questions to guide you in video and for the discussion [PDF]
  • Lecture slides [PDF, with password]



Thursday, May 21

Ascencion Day ("Himmelfahrt") - No class


Tuesday, May 26
  • Recap: Poisson-Boltzmann
  • Poisson-Boltzmann for complex nucleic acids
  • Comparison: experimental data and Poisson-Boltzmann
  • MD simulations for nucleic acid-ion interactions
  • Introduction to single-molecule force manipulation techniques
  • DNA as an isotropic elastic rod
  • Lecture slides [PDF, with password]


Thursday, May 28
  • Coronaviruses: Basic biology and the current pandemic
  • Short answers to the questions guiding the discussion of "Coronavirus 101" by Britt Glaunsinger [PDF]
  • Lecture slides [PDF, with password]



Tuesday, June 02

Pentecost ("Pfingsten") - No class


Thursday, June 4
  • Recap: Single-molecule stretching experiments
  • Isotropic rod model
  • Worm-like chain
  • Lecture slides [PDF, with password]


Tuesday, June 09
  • Freely-jointed chain: root mean end-to-end distance
  • Freely-jointed chain under external force
  • Force-extension experiment for DNA
  • Lecture slides [PDF, with password]


Thursday, June 11
Feast Corpus Christi ("Fronleichnam") - No class


Tuesday, June 16
  • 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 18
  • Recap: Twisting DNA and torsional stiffness
  • Magnetic torque tweezers
  • DNA bending and twisting stiffness
  • Twist-stretch coupling 
  • Lecture slides [PDF, with password]


Tuesday, June 23
  • 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 25
  • Energy in biological systems
  • Enzyme-catalyzed reactions in biological systems
  • Michaelis-Menten theory of enzymatic reactions
  • Lecture slides [PDF, with password]


Tuesday, June 30
  • Pointers on giving scientific presentations
  • Michaelis-Menten, revisted: kcat/Km regime, point of half-maximal rate, saturation regime
  • Diffusion-limited enzymes
  • Super-diffusive enzymes
  • Michaelis-Menten at the single-molecule level
  • Lecture slides [PDF, with password]



Thursday, July 2


Tuesday, July 07
  • DNA topology
  • White's theorem: Lk = Tw + Wr
  • Organization and processing of genomes
  • Nucleosome structure and dynamics
  • Lecture slides [PDF, with password]



Thursday, July 09
  • Discussion PS7
  • Life at low Reynolds number
  • Diffusion coefficient, Einstein-Stokes relationship, Langevin equation
  • Swimming bacteria: Scallop theorem, Purcell's swimmer, runs & tumbles
  • Lecture slides [PDF, with password]


Tuesday, July 14
  • Organization and processing of genomes, continued
  • Phase transitions in biological systems
  • Discussion: What the Drosten and coworkers viral load study can teach us about scientific publishing
  • Lecture slides [PDF, with password]


Thursday, July 16
  • Guest lecture by Prof. Thorben Cordes
  • Time and length scales in biology
  • Förster Resonance Energy Transfer (FRET)
  • Protein Dynamics and ligand binding models
  • Lecture slides [PDF, with password]


Tuesday, July 21
  • Student presentations "Biophysics TED Talks"
  • Schedule [PDF]


Thursday, July 23
  • Student presentations "Biophysics TED Talks"
  • Schedule [PDF]


Tuesday, July 28
  • 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 during August 3-10, 2020
  • See the "Overview" tab for details about how to sign up, the exam schedule, and exam results.