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 17, 2024
Problem set 1, due Thursday, Oct. 31, 2024
02 Energy scale of macromolecule interactions, Oct 24, 2024
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 14, 2024
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
- 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
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. 7, 2024 (SR44)
- 03-1 Enthalpy-entropy analysis of protein-DNA interactions
- 03-2 Entropy contributions to interactions between macromolecules
- coordinates nucleosome.pdb
- VMD molecular visualization program
- VMD tutorial
- Coordinates of ubiquitin for VMD tutorial
05 Simple ligand binding, Nov 14, 2024 (SR41)
Problem set 3, due Thursday, Nov 28, 2024
Additional reading
- Introduction to ligand binding (Rippe, 1997)
- Michaelis-Menten Equation
- Cantor & Schimmel Chapter 15 - Ligand binding at equilibrium
06 Complex ligand binding, Nov 21, 2024 (SR41)
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 (SR41)
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 5, 2024 (SR41) (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 Jan 9, 2025
09 Diffusion, protein transport and compartmentalization, Dec 12, 2024 (SR41)
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)
Problem set 5, due Jan 16, 2025
************************************ Christmas break **********************************
*********************** No lecture on Thursday, Dec 19, 2024 **********************
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10 Measuring protein-DNA/chromatin interactions in living cells, part I, Jan 9, 2025 (SR41)
Problem set 6, due Jan 30, 2025
11 Formation of cellular subcompartments by phase separation processes, Jan 16, 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
Problem set 5, due Tuesday, Feb 13, 2024
12 Measuring protein-DNA/chromatin interactions in living cells, part II, Jan 23, 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
11 Protein-protein interactions at a distance, Jan 30, 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 6, 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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