BIOQUANT > Research Groups > Genome Organization & Function > Teaching > Interactions of Proteins and Nucleic Acids I (1-8)
Interactions of Proteins and Nucleic Acids - Biophysical Concepts and Theoretical Descriptions
01 The molecular length and time coordinate system, Oct 14, 2025
Problem set 1, due Thursday, Oct. 28, 2025
- Reference solution to problem set 1
- Grading scheme problem set 1
02 Energy scale of macromolecule interactions, Oct 21, 2025
- 02-1 Time and length scales
- 02-2 Energy scale of macromolecule interactions
- 02-3 Intro protein-DNA interactions
Additional information
- Cell Chemistry and Bioenergetics (Ch. 2, MBC Alberts et al.)
- Proteins (Ch. 3, MBC Alberts et al.)
- Database https://bionumbers.hms.harvard.edu
- R. Milo & R. Philipps, Cell Biology by the Numbers, 2015. Download pdf draft
- Dill, K.A., Ghosh, K., and Schmit, J.D. (2011). Physical limits of cells and proteomes. Proc Natl Acad Sci USA 108, 17876–17882.
- Summary nonbonding interactions (van Holde) (14 MB)
- Key reference: The hydrophobic effect (Tanford 1962)
- Protein structure, stability and solubility in water and other solvents (Pace et al. 2004)
- Sharp, K.A. & Honig, B. (1990). Electrostatic interactions in macromolecules: theory and applications. Annu. Rev. Biophys. Biophys. Chem. 19, 301-32.
- Mass of human chromosomes, Bhartiya 2021 Chromosome Res (p. 108-109)
03 Introductio protein-DNA interactions, Oct 31, 2024
Problem set 2, due Thursday, Nov 18, 2025
- Coordinates of the structure "DNA_unusual.pdb"
- Coordinates of the structure "“B-DNA_20mer.pdb"
- ChimeraX structure viewer
- Reference solution to problem set 2
- Grading scheme problem set 2
Additional reading DNA and protein structures
- DNA, chromosomes and genomes (Ch. 4, MBC Alberts et al.)
- Control of gene expression (Ch. 7, MBC Alberts et al.)
- The DNA double helix (Watson, J.D., andF.H. Crick. 1953. A structure for deoxyribose nucleic acid. Nature 171:737-738)
- B-DNA 12mer Crystal structure (Drew, H.R., R.M. Wing, T. Takano, C. Broka, S. Tanaka, K. Itakura, andR.E. Dickerson. 1981. Structure of a B-DNA dodecamer: conformation and dynamics. Proc Natl Acad Sci U S A 78:2179-2183)
- Kneale, G., Brown, T., Kennard, O. & Rabinovich, D. (1985). G·T base-pairs in a DNA helix: the crystal structure of d(G-G-G-G-T-C-C-C). J. Mol. Biol 186, 805-14.
- Review on Z-DNA (Rich, A., andS. Zhang. 2003. Timeline: Z-DNA: the long road to biological function. Nat Rev Genet 4, 566-572)
- Paper by Schalch et al on Tetranucleosome structure
Additional reading Lac repressor
- Structure analysis of Lac repressor and its complexes with DNA
- Review of Lac repressor structures (Charalampos, 2004)
- Specific vs unspecific complex, NMR structure
- Comment Peter von Hippel on NMR structure
- Thermodynamic analysis of specific and unspecific LacI-DNA complexes
Other 3D structure coordinates in pdb format
- ChimeraX structure viewer
- TATA box binding protein (TBP) with DNA
- TBP protein alone
- 3D coordinates of B-DNA 12mer with K+ counter ions from crystal structure
- DNA with unusual base pair
- Tripeptide
- RCSB Protein Data Bank (pdb)
- Lac repressor pdb coordinates (protein only)
- Lac repressor + DNA pdb coordinates
- Lac repressor complete dimer + SymL DNA, crystal structure
- Lac repressor head piece + SymL DNA, NMR
- Lac repressor head piece + O1 DNA, NMR
- Lac repressor head piece + unspecific DNA, NMR
- Lac repressor head piece + Operator DNA
- TATA box binding protein (TBP) + promoter DNA
- CAP (Catabolite Gene Activator Protein) + DNA
- Lambda C1 repressor + operator DNA
- GCN4 + AP-1 DNA
- Coordinates for nucleosome
Additional reading on thermodynamics of protein binding to DNA
- Key reference "Induced fit model" site specific protein binding to DNA (Spolar & Record, 1994)
- Comment 1: Peter von Hippel on Spolar & Record paper Comment 2: Stephen Burley on Spolar & Record paper
- Key reference Entropy/Enthalpy in Protein-DNA complexes (Jen-Jacobson, 2000)
04 Thermodynamics of protein-DNA interactions, Nov. 4, 2025
- 04-1 Enthalpy-entropy analysis of protein-DNA interactions
- 04-2 Entropy contributions to interactions between macromolecules
****************** No lecture on Tuesday, Nov 11, 2025 *******************
05 Simple ligand binding, Nov 18, 2025
Problem set 3, due Thursday, Dec 2, 2025
- Reference solution to problem set 3
- Grading scheme problem set 3
Additional reading
- Introduction to ligand binding (Rippe, 1997)
- Michaelis-Menten Equation
- Cantor & Schimmel Chapter 15 - Ligand binding at equilibrium
06 Complex ligand binding, Nov 25, 2025
Additional reading
- Allostery from Athel Cornish-Bowden "Fundamentals of Enzyme Kinetics"
- Changeux, J.-P. (2013). 50 years of allosteric interactions: the twists and turns of the models. Nat Rev Mol Cell Biol 14, 819–829.
- Phillips, R. (2015). Napoleon Is in Equilibrium. Annu Rev Condens Matter Phys.
- Gregor, T., Tank, D.W., Wieschaus, E.F., and Bialek, W. (2007). Probing the limits to positional information. Cell 130, 153–164
- Copasi kinetics simulation program
- Copasi parameter text files with extension ".cps") | remodeler nucleosome translocation | Michaelis-Menten Kinetics | NF-kappaB Oscillation
- The B-Z-DNA junction (Ha, S.C., K. Lowenhaupt, A. Rich, Y.G. Kim, and K.K. Kim. 2005. Crystal structure of a junction between B-DNA and Z-DNA reveals two extruded bases. Nature 437:1183-1186
- Coordinates B-Z-DNA junction with Z-DNA binding peptide
07 Intro chromatin networks, Nov 28, 2024
Additional reading
- Chromatin intro: DNA, chromosomes and genomes (Ch. 4, MBC Alberts et al.)
- Allis & Jenuwein (2016). The molecular hallmarks of epigenetic control. Nat Rev Genet 17, 487–500.
- Cremer, T., Cremer, M., Hübner, B., Strickfaden, H., Smeets, D., Popken, J., Sterr, M., Markaki, Y., Rippe, K., and Cremer, C. (2015). The 4D nucleome: Evidence for a dynamic nuclear landscape based on co-aligned active and inactive nuclear compartments. FEBS Lett 589, 2931–2943.
- Maeshima, K., Ide, S., Hibino, K., and Sasai, M. (2016). Liquid-like behavior of chromatin. Curr Opin Genet Dev 37, 36–45.
- Moazed, D. (2011). Mechanisms for the inheritance of chromatin states. Cell 146, 510–518.
- Struhl, K. (2014). Is DNA methylation of tumour suppressor genes epigenetic? eLife 3, e02475.
08 Modeling epigenetic regulation, Dec 2, 2025 (Fabio Nickels)
Simulating epigenetic chromatin states
The simulations are run with a Jupyter notebook. For installing the Jupyter software first download the Anaconda installer for your operating system from https://www.anaconda.com/download/success and install Anaconda on your computer. Then start the Anaconda-Navigator app and open Jupyter notebook, which will run in your browser. From there open the Bistable_chromatin_model notebook and run it.
Download (revised version from Dec 6): Jupyter notebook Bistable_chromatin_model_rev.ipynb
Problem set 4, due Dec 16, 2025
- Reference solution to problem set 4
- Grading scheme problem set 4
09 Diffusion, protein transport and compartmentalization, Dec 9, 2025
Additional reading
- Hydrodynamics Review by Bloomfield
- Key reference: Berg & von Hippel, Diffusion controlled reactions
- Berg & von Hippel, review on protein target location
- Halford & Marko, review on protein target location
- Halford, measurements on target location by restriction enyzmes
- Widom, review on protein target location
- Shimamoto, review on 1D diffusion
- Genome dynamics and stability (Wachmuth et al. 2008)
- Transcription factor binding on chromatin (Trojanowski & Rippe, 2022)
- Structure function relationships in eukaryotic transcription factors (Ferrie, 2022)
10 Measuring protein-DNA/chromatin interactions in living cells, part I, Dec 16, 2025
Problem set 5, due Jan 20, 2025
- Reference solution to problem set 5
- Grading scheme problem set 5
************************************ Christmas break **********************************
*********************** No lecture on Thursday, Dec 19, 2024 **********************
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11 Formation of cellular subcompartments by phase separation processes, Jan 13, 2025
Additional reading
- Banani et al, review on liquid-liquid phase separation
- Hyman et al, review on liquid-liquid phase separation
- Erdel & Rippe, review on phase separation to form chromatin compartments
- Michieletto et al, simulation of collapsed chromatin globules
- Chung et al, review on PML bodies
12 Measuring protein-DNA/chromatin interactions in living cells, part II, Jan 20, 2025
Additional reading
- Protein mobility maps, Erdel et al. 2010
- The interior of a cell from a moving protein's point of view
- Super-enhancer liquid droplets, Hnisz 2017, Cell
- Insulator mechanisms, Gaszner 2006 Nat Rev Genet
- Real-time observation of light-controlled transcription in living cells, Rademacher et al 2017
Problem set 6, due Feb 3, 2025
- Reference solution to problem set 6
- Grading scheme problem set 6
11 Protein-protein interactions at a distance, Jan 27, 2025
Additional reading
- Looping mediated interactions
- Protein contacts mediated by looping of DNA and RNA & Chromatin conformation capture (3C)
- Key reference: Rippe, Looping mediated contacts on nucleic acids
12 Integrating imaging and omics readouts, Feb 3, 2025
Additional reading
- Chromosome conformation capture assay, Dekker 2002 Science
- HiC 3D folding maps, Rao 2014 Cell
- Movie HiC origami (56 Mb)
- Single cell HiC, Nagano 2013 Nature
- Insulator mechanisms, Gaszner 2006 Nat Rev Genet
- Nucleation & loopiong mechanisms, Erdel 2013 Ann N Y Acad Sci
- Position weight matrixes for TF binding sites, Wasserman 2004 Nat Rev Genet
- Measuring protein-chromatin binding by ChIP-seq, Poorey 2013 Science
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