Download Coarse-Graining of Macromolecules

Lecture 2
(Block et al.)
(Wuite et al.)
Rob Phillips
California Institute of Technology
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: 50-1000nm
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.)
(Lieber et al.)