Lectures
Week 1: Tree structures, Sets, and Descent
Note: Ive added some extra links based on questions I couldnt answer during the lectures. These added materials are in green.
There are two very basic ideas which are the foundations of biology. The first is Darwins idea, that all organisms are related by descent from common ancestors. They differ by inherited mutations, producing hierarchical tree-like structures of relatedness. In the first week of this course, we will explore the structure of biological molecules (particularly nucleic acids and proteins) with this idea firmly in mind.
Day 1
Read MIT chapters Chemistry Review and Cell Biology, subsections 1-7, Read Stryer Chapter 2: Biochemical Evolution
Learning Objectives: 1) To understand why carbon is uniquely suited to build large complex molecules needed to support life. 2) To understand why liquid water is uniquely suited as a medium for biological chemistry. 3) To see that life must have arisen in a series of steps, from small simple organic molecules through self-replicating RNAs to the current form of membrane-bound cells full of DNA libraries and protein industrial machinery.
Tree structures
phylogeny vs. ontogeny
Origins of Life
tree of life (berkely link)--one ancestor species, each species expresses genes which have diverged over time.
analogies to number sets
cell fate lineage (wormatlas.org) --one ancestor individual, each cell expresses only a subset of inherited genes.
learner.org
why carbon? (WebElements)
chemical evolution (Stryer timeline)
Boron: electron deficient
reducing environments and redox reactions
Nitrogen: too electron rich (N-N bond ~ 171kJ/mol)
C-C ~ 348kJ/mol
Silicon
too big (Si-Si bond ~ 177kJ/mol)
Phosphorus: less stable than nitrogen
too stable (Si-O bond ~ 369kJ/mol)
precursors of life
redox history
the RNA world
membranes and compartments
Aqueous Solutions
hydrogen bonding
hydrophilic vs. hydrophobic
water molecule
in liquid water
acids and bases
titrations & buffers (Voet Ch2)
Thermodynamics
amino acids--glycine (Voet Ch4)
3 laws
Day 2
energy OF THE WHOLE UNIVERSE is conserved
Gibbs free energy
entropy OF THE WHOLE UNIVERSE always increases
entropy of a perfect crystal at 0K is 0
state functions (temperature, pressure, volume, ENERGY)
chemical equilibrium
enthalpy (NASA link)
entropy
spontaneity (sch4u link)
Read Stryer Chapter 4: Exploring Proteins , Stryer Chapter 6: Exploring Genes
Learning Objective: Before accepting the numbers some experimentalist has generated into our favorite model, wed like to have some idea as to how he generated them. Today, well discuss a few particular techniques that relate to the laboratory section of the course.
Techniques of Purification
opening cells
mechanically (with a blender or by freezing)separating components (Voet Ch6)
with enzymes (Voet Ch 15) (ProteinDataBase)
by sizeread MIT chapter Large Molecules
by charge
by affinity
what is a covalent bond?electronegativity
comparison with ionic bonds
electronegativity defined
nucleic acids (phosphodiester bonds)delta G ~ +25kJ/mol
4 monomers (MIT nucleic acids)carbohydrates
RNA pol 1 (Stryer Fig 28.1)
glycosidic linkages (MIT carbohydrates) delta G ~ +15kJ/molproteins (peptide bonds) deltaG ~ +10kJ/mol
branched carbohydrates (Stryer Fig11.2)
20 monomers (MIT amino acids)lipids
mechanism (Stryer Fig 29.3)
types (MIT lipids)Day 3
synthesis more complicated
sequencing reactionsfrom NCGR
replication
in bacteria (Kaisers microbiology page)mobile genetic elements
crossing over during diploid meiosis from Access Excellence
making RNA (RNA polymerase) (Stryer Ch28.1)postprocessing in prokaryotes
initiation (Stryer Fig5.4)elongation (stryer Fig5.25)
promoters with more G-C content are transcribed less often
termination (Stryer Fig5.28)
why are there introns? (readGenomes Ch15.32)
three roles of RNA (Lodish Fig4.4)
the message, mRNAinitiation
the ribosome, rRNA (Stryer Ch29.3)
the adaptor, tRNA (ProteinDataBank tRNA) (Lodish Fig4-26)
initiation sequences (Stryer Fig29.20)elongation (Lodish elong movie)
methionine (Lodish Fig4.5) (Stryer Fig29.26)
initiation (Lodish Fig4.5.1)
protein cleavage (Stryer Ch10.5)protein degradation
side chain modifications
cysteine disulfide bonds (Stryer Fig3.21)
glycosylation (Stryer Ch11.3.1)
acetylation of histones (Lodish Fig10.58)
phosphorylation (Cooper fig13.22)(Stryer Ch10.4)
lysosomes are full of nonspecific proteasesDay 5
ubiquitin (Lodish Fig3.18)
N terminal residues partly determine half-life; note that these are not grouped as in the property table (MIT Large Molecules). Leu, Ile, and Gly are all small and hydrophobic, yet they span the range.
Met, Ser, Ala, Thr, Val, Gly > 20 hours
Ile, Glu, Tyr, Gln ~ 20-30 minutes
Phe, Leu, Asp, Lys, Arg ~ 2-3 minutes
helices
single nucleosome3-D structure of proteins shows hierarchy (Lodish Fig3.4)
chromatin packing
amino acid reminder (Lodish Fig3.2)
why these 20? (Stryer Fig3.17)secondary structure
spontaneous folding (Lodish Fig3-13) (Stryer Fig3-58)quaternary structure, or multiple-subunit proteins (Stryer Ch3.5)
assisted folding (Lodish fold movie)
binding a small ligand (cAMP)
functional domains within a single polypeptide chain (Lodish Fig3-10)
Do exons line up with domains? (Genomes Fig15.19)short peptide sequences (Stryer Fig3.55)
silent mutationscase study: Green Fluorescent Protein
base substitutions (Stryer Table5.4)why not sequence proteins?
amino acid substitutions
proteins cant replicate themselves
youd miss all the regulatory sequences (promoters, etc.)
physics of fluorescence from Molecular Probes
PDB molecule of the month GFP
GFP structure from Fan Yang at Rice