Lecture 2 Rob Phillips California Institute of Technology (Block et al.) (Wuite et al.)

Biological Structure: Spatial Hierarchy Structure exists at many length scales → structural hierarchies Bond lengths: ~1-3Å Amino Acids: ~1nm Proteins: 2-5nm Macromolecular assemblies: 5-50nm Organelles: nm Cells: microns and beyond Tissues

Biological Structure: Spatial Hierarchy Structure exists at many length scales → structural hierarchies. Each of these scales in the hierarchy is amendable to modeling. Not surprisingly, all of the usual multiscale challenges are present with a vengeance because often different levels in the hierarchy cannot be isolated.

Biological Processes: Temporal Hierarchy Processes exists at many time scales → hierarchies of processes. Not surprisingly, all of the usual multiscale challenges are presence with a vengeance because often different levels in the hierarchy cannot be isolated. (Chan and Dill)

Procaryotic Cells - Bacteria

Eucaryotic Cells Yeast cells

Cellular Contents

The Great Polymer Languages

Sugars glucose

Lipids and Cellular Compartments

Lipids and the Architecture of Life Lipids are neurotic molecules with polar (hydrophilic) head groups and hydrocarbon (and hydrophobic) tails. These molecules are one of the simplest examples of one of the most profound ideas to preside over the living world – HYDROPHOBICITY.

Lipid Bilayers and Membranes A consequence of the amphiphilic character of lipid molecules is the sequestering of the hydrophilic and hydrophobic parts. The structural solution that permits this sequestering is lipid bilayers.

Amino Acids and Proteins Amino Acids are the building blocks of Proteins

Biological Structure: Protein Structure Structural Levels Primary (amino acid sequence) Secondary (α-helices, β-strands) Tertiary (domains) Quaternary (active sites)

Protein Function 1

Enzymes and Glycolysis: Protein Function 2

Case Studies in Protein Structure: Protein Diversity Proteins come in a variety of shapes and sizes. Enzymes are usually huge in comparison with the molecules for which they catalyze reactions (i.e. their substrates). Question: Is there a simple scaling of protein size with the number of amino acid residues? Close packing leads to: Random walk description of polymer leads to:

Nucleotides and Nucleic Acids Sugars ribose and deoxyribose each react with a base and a phosphate to form nucleotides. Nucleotides polymerize to form nucleic acids RNA and DNA. Certain Nucleotides (ATP) carry chemical energy

DNA as the Carrier of Genetic Information

Cartoons and Biological Processes: The Central Dogma

Reduced Description of Protein Structure

Single Molecule Experiments: A Reminder There are a variety of techniques for measuring the relation between force and extension for single molecules. This domain has been dubbed dynamical force spectroscopy.

DNA as a Case Study in Single Molecule Biomechanics Force-extension curves for DNA have served as a testbed for the quantitative analysis of the deformation of macromolecules. (Lieber et al.)