lecture1 handout
TRANSCRIPT
1
BCMP 201Protein biochemistry
BCMP 201
Protein biochemistry with emphasis on the interrelated roles of protein structure,catalytic activity, and macromolecular interactions in biological processes.The course is intended to provide the core background and perspectiverequired to consider and dissect biological problems at a mechanistic, molecular level.
2
Central dogma of molecular biology:
DNA RNA protein
Central dogma of molecular biology:
DNA RNA protein
Central dogma of protein biochemistry:
sequence structure function
3
sequence
structure
function
sequence alignmenthomology modelinghands-on session (Blast, other bioinformatics tools)
physical interactions (covalent, noncovalent)1ary, 2ary, 3ary, 4ary structuremolecular visualizationhands-on session (Pymol, other visualization tools)
enzymatic mechanismschemical kinetics, thermodynamics
BCMP 201
Tuesdays 9:00 - 10:30 am: Lecture (Cannon Room, C Building)
Wednesday 4:30 - 6:00 pm: Methods lecture (TMEC)Discussion SectionHands-on session
4
BCMP 201
Discussion section (4x)
- Each section will be guided by two TF’s/instructors- Two research papers will be discussed- Two students will present presentation, each on one of the two papers- Papers will be posted one week in advance, with discussion questions
BCMP 201
Problem sets (5x)
- Each problem set will be posted one week before it’s due (Wednesdays)- Students can work together
5
BCMP 201
Final exam
- 24-hr take home- Students cannot work together
BCMP 201
Final grade
30% section presentation30% problem sets30% final10% section participation
6
BCMP 201
Course website
http://cmcd.med.harvard.edu/activities/bcmp201/class
Course directors
Antoine van Oijen: [email protected] Chou: [email protected]
Teaching fellows
Irene Kim (head TF)Scott AokiAmanda RiceRebecca RoushMichelle Stewart
Lecture 1: physical interactions, primary structure
• Length, time, and energy scales
• Covalent bonds
• Noncovalent bonds
• Amino acids and their basic properties
7
Length scales
8
Length scales
Insulin (pdb id: 2hlu; 5.8 kDa) Ribosome (1fjf + 1jj2; ~ 4 Mda)
10 nm
Time scales
9
Energy scales
1 kJ/mol ~ 0.24 kcal/mol
Energy scales
(www.calorieking.com)1 kJ/mol ~ 0.24 kcal/mol
1 mol of glucose = 180 grams180 g x 16 kJ = 2880 kJ/mol(or about 691 kcals)
10
Energy scales
1 kJ/mol ~ 0.24 kcal/mol
ADP ATP
Total quantity of ATP + ADP in human body is about 0.1 mol (about 50 g)
Energy made available by hydrolysis ATP into ADP: only ~ 50 kJ/mol
Where does energy to power cells come from?
Every ATP is recycled ~ 1,000 times/day(burning the equivalent of your body weight in ATP on any given day…)
Molecular interactions and structural hierarchy
Covalent bonds
Hydrogen bonds
Hydrophobic effect
Hydrogen bondsElectrostatic interactionsHydrophobic effect
1ary
2ary
3ary
4ary
11
Covalent bonds
(Image from: http://serc.carleton.edu/images/usingdata/nasaimages/periodic-table.gif)
Maximum # ofelectrons in outer shell
28818
Element: H C N O S
# of electrons needed to fill outer shell: 1 4 3 2 2
Lewis notation: H C N O S
# of electronsin outer shell
. .. .. ... ... .. ... . . .. ..
Covalent bonds
Atoms will favor as many bonds to fill up outer electron shells (the ‘octet’ rule)
ammonia water methane oxygen
nitrogen
12
Common functional groups
Covalent bond lengths and energies
Bond Distance Energy (Å) (kJ/mol)
O-H 0.96 462C-H 1.10 416C-O 1.43 353C-N 1.52 294S-S 2.02 214
C=O 1.20 714C=C 1.34 613
13
Electronegativity
Electrons are shared unequally in polar covalent bonds
Electronegativity values
Bonding geometry
Not only stoichiometry is important, also geometry
14
Configuration: chiral and achiral
Configuration: stereoisomers
15
Configuration versus Conformation
Configuration: fixed spatial arrangementConformation: spatial arrangement that can change due to rotation around bonds
Amino acids
Amino acids link together to form proteins
Amino acid Peptide
16
Amino acids
Amino acids link together to form proteins
Amino acid Peptide
aminogroup
carboxylgroup
sidegroup
Stereoisomerism in amino acids
Amino acids in proteins are L-stereoisomers
17
Structures of the 20 common amino acids
Hydrophobic amino acids
18
Aromatic amino acids
Polar amino acids
19
Disulfide bonds
Acidic amino acids
20
Basic amino acids
Glycine
21
Side-chain pKa’s
Histidine has pKa close to neutral
Peptide bond formation
α-amino group is good nucleophile, but -OH is poor leaving group:At room temperature peptide-bond formation does not occur spontaneously
22
The peptide bond is planar
Conformational freedom in polypeptides
2 rotational degrees of freedom: Φ and Ψ
(Lecture 2: backbone conformations; secondary structure)
23
Conformational freedom in polypeptides
Steric clashing of side groups prevents adjacent amino acids to be in the cis conformation
Conformational freedom in polypeptides
Glycine can adopt backbone conformations that aresterically impossible with other a.a.’s
Proline can undergo cis-trans isomerization more easilythan other a.a.’s
24
Covalent and noncovalent interactions
Electrostatic forces
Coulomb’s law:
!
F =q
1q
2
r 2D+ -
rq1 q2
D is dielectric constant of medium (D=1 for vacuum D=80 for water)
When in direct contact salt bridge
Electrostatic interactions effectivelyscreened by water
25
Hydrogen bonding
Hydrogen bonding
Oxygen is very electronegative Stabilization of ice by H-bonding
26
Hydrogen bonding
H-bonds are highly directional
Hydrophobic effect
Apolar molecules tend to stick together to maximize hydrogen bonding in solute
No physical interaction between hydrophobic molecules; instead a consequence ofsolute properties (entropy versus enthalpy in a few weeks)
27
Hydrophobic effect
Amphiphatic molecules (polar on one end,apolaron the other) will self aggregate
Driving force in protein folding(hydrophobic core; hydrophilic outside)
Van der Waals forces
Induced dipole-dipole interactions caused bymovements of nuclei in electron clouds
28
Van der Waals forces
Lennard-Jones potential:
!
E(r ) =A
r12"
B
r6
Van der Waals surfaces