protein structure and energetics
DESCRIPTION
Adam Liwo Room 406 Faculty of Chemistry, University of Gdańsk phone: 58 345 5430 (or 5430 within the University) email: [email protected]. Protein Structure and Energetics. Course language: English. Schedule and requirements. - PowerPoint PPT PresentationTRANSCRIPT
Protein Structure and Energetics
Adam Liwo
Room B325Faculty of Chemistry, University of Gdańsk
phone: 58 523 5124 (or 5124 within the University) email: [email protected]
Course language: English
Schedule and requirements
• Mondays, 8:15 – 10:00, room C209, Faculty of Chemistry, University of Gdańsk
• 2 problem sets
• Final exam
Scope of this course
1. Levels of structural organization of proteins.
2. Quantitative description of protein geometry.
3. Secondary and supersecondary structure.
4. Tertiary and quaternary structure.
5. Schemes of protein-structure classification.
6. Interactions in proteins and their interplay.
7. Folding transition as a phase transition.
8. Foldability and the necessary conditions for foldability.
9. Misfolding and aggregation; formation of amyloids.
10. Experimental methods for the investigation of protein folding.
11. Atomistic-detailed and coarse-grained models and force fields for protein simulations.
Literature
• C. Branden, J. Toze, „Introduction to Proten Structure”, Garland Publishing,1999
• G. E. Schultz, R.H., Schrimer, „Principles of Protein Structure”, Springer-Verlag, 1978
• Ed. J. Twardowski, „Biospektroskopia”, cz. I, PWN, 1989
• I. Z. Siemion, „Biostereochemia”, PWN, 1985
Proteins: history of view
• 1828: By syntesizing urea, Friedrich Woehler voided the vis vitalis theory, opening roads to modern organic chemistry.
• 1850’s: First amino acids isolated from natural products
• 1903-1906: By hydrolysis of natural proteins, Emil Fischer proves that they are copolymers of amino acids (strange, but none of his so fundamental papers earned more than ~60 citations!).
• 1930’s and 1940’s: proteins are viewed as spheroidal particles which form colloidal solution; their shape is described in terms of the long-to-short axis ratio.
• 1930’s: it is observed that denaturated proteins do not crystallize and change their physicochemical and spectral properties.
Proteins: history of view (continued) • 1940’s: evidence from X-ray accumulates suggesting that
fibrous proteins such as silk and keratin might have regular structure.
• 1951: Pauling, Corey, and Branson publish the theoretical model of protein helical structures.
• 1960: Laskowski and Scheraga discover anomalous pKa values in ribonuclease, which suggest that the acidbase groups are shielded from the solvent to different extent.
• 1963: First low-resolution X-ray structure of a protein (horse hemoglobin) published by the Perutz group.
• Today: 68840 structures of proteins, nucleic acids, and sugars in the Protein Data Bank.
Protein shapes from viscosity data
ba
Polson, Nature, 740, 1936
Pauling’s model of helical structures
First structure: hemoglobin (X-ray)
Example of a recently solved structure: DnaK chaperone from E.coli (2KHO)
Levels of protein structure organization
The primary structure (Emil Fischer, 1904)
H3N+-Gly-Ile-Val-Cys-Glu-Gln-..........-Thr-Leu-His-Lys-Asn-COO-
N-terminusC-terminus
-amino acids are protein building blocks
-amino acids: chemical structure
Classification of amino-acids by origin
Amino acids
Natural Synthetic
Proteinic (L only) Non-Proteinic (D and L)
Primary (coded) Secondary (post-translational
modification)
Tertiary (e.g., cystine)
Endogenous Exogenous
Amino-acid names and codesSynthesized in humans Supplied with food
Name Code Name Code
Alanine Ala A Histidine His H
Arginine Arg R Isoleucine Ile I
Asparagine Asn N Leucine Leu L
Aspartic acid Asp D Lysine Lys K
Cysteine Cys C Methionine Met M
Glutamine Gln Q Phenylalanine
Phe F
Glutamic acid Glu E Threonine Thr T
Glycine Gly G Tryptophan Trp W
Proline Pro P Valine Val V
Serine Ser S
Tyrosine Tyr Y
The peptide bond
Venn diagram of amino acid properties
T C A G
T
Phe
Ser
Tyr Cys TC
Leu TerTer A
Trp G
C Leu ProHis
ArgTC
Gln AG
AIle
ThrAsn Ser T
C
Lys ArgA
Met G
G Val AlaAsp
GlyTC
Glu AG
The "Universal" Genetic CodeIn form of codon, Left-Top-Right (ATG is Met)
Atom symbols and numbering in amino acids
Chirality
Enantiomers
Phenomenological manifestation of chiraliy: optical dichroism (rotation of the plane of polarized light).
Determining chirality
Highest oxidation state
Chain direction
The CORN rule
Absolute configuration: R and S chirality
Rotate from „heaviest” to „lightest” substituent
R (D) amino acids S (L) amino acids
Representation of geometry of molecular systems
• Cartesian coordinates• describe absolute geometry of a system,
• versatile with MD/minimizing energy,
• need a molecular graphics program to visualize.
• Internal coordinates• describe local geometry of an atom wrt a selected reference
frame,
• with some experience, local geometry can be imagined without a molecular graphics software,
• might cause problems when doing MD/minimizing energy (curvilinear space).
z
x yxH(6)
yH(6)
Cartesian coordinate system
Atom x (Å) y (Å) z (Å) C(1) 0.000000 0.000000 0.000000 O(2) 0.000000 0.000000 1.400000 H(3) 1.026719 0.000000 -0.363000 H(4) -0.513360 -0.889165 -0.363000 H(5) -0.513360 0.889165 -0.363000 H(6) 0.447834 0.775672 1.716667
zH(6)
C(1)
O(2)
H(3)
H(4)
H(5)
H(6)
Internal coordinate system
i dij ijk ijkl j k lC(1) O(2) 1.40000 * 1H(3) 1.08900 * 109.47100 * 1 2H(4) 1.08900 * 109.47100 * 120.00000 * 1 2 3H(5) 1.08900 * 109.47100 * -120.00000 * 1 2 3H(6) 0.95000 * 109.47100 * 180.00000 * 2 1 5
C(1)
O(2)
H(3)
H(4)
H(5)
H(6)
Bond length
Bond (valence) angle
Dihedral (torsional) angle
The C-O-H plane is rotated counterclockwise about the C-O bond from the H-C-O plane.
Improper dihedral (torsional) angle
Bond length calculation
jizzyyxxd ijijijij 222
xi yi
zi
xj
zj
xj
jkji
jkij
jkjijkjijkjiijk
jk
jk
ji
ji
jkji
jkji
dd
zzzzyyyyxxxx
uu ˆˆ
cos
ijk
i
j
k
Bond angle calculation
i
j
k
l
ijkl
a
b
jk
jkijklijkl
ba
ba
ba
ba
sincos
ba
Dihedral angle calculation
The vector product of two vectors
ba
a
b
ab
xyyxz
xzzxy
yzzyx
baba
baba
baba
ba
ba
ba
baab
baba
sin
xyyxxzzxyzzy
zyx
zyx
babababababa
bbb
aaa
kji
kji
ba
Some useful vector identities
cbabaccabcba
0aa
abba
i
j
k
'a
a
ijk ijk
ijkjiijkji
ijkjk
ji
ijkjk
jiijk
dd
jkd
dji
jkd
dji
jk
jk
ji
sincos1
cos
cos180cos'
'
22
aaa
a
a
aa
i
j
k
l
ijkl
a
b
ba
ijkklijkjk
kl
ijkjiijkjk
ji
dkjd
dkl
djkd
dji
sincos
sincos
bb
aa
jklijk
jklijkklij
ijkl
ddklji
sinsin
coscos
cos
ba
ba
jklijkkljkij
ijkl
jklijk
jklijkklij
ijkl
ddd
jkklji
ddklji
sinsinsin
sinsin
coscos
cos
ba
ba
j
k
l
ijkl
a
b
ba
yx
z
342642626H(6)
342642626H(6)
42626H(6)
sinsin
cossin
cos
dz
dy
dx
3426
426
d26
C(1)
H(3)
O(2)
H(4)
H(5)
H(6)
Calculation of Cartesian coordinates in a local reference frame from internal coordinates
Need to bring the coordinates to the global coordinate system
localTglobal
locali
locali
locali
iii
iii
iii
globali
globali
globali
z
y
x
eee
eee
eee
z
y
x
RER
332313
322212
312111
i-2
i-1
i
i+1
di-1
di
di+1
i-1
i
i+1
i+2
i
Polymer chains
i-2
i-1
i
i+1
di-1
di+1
i-1
i+2
i-1
i+1
i-1
i+1
pi-1
1112134231
111213423
331214
2213
112
01
nnnnnnn
iiiiiii
rpTTRTRTRr
rpTTRTRTRr
rpTTRr
rpTr
rpr
pr
ii
iiiii
ii
i
i
i
d
cossin0
sincos0
001
100
0cossin
0sincos
0
0 RTp
For regular polymers (when there are „blocks” inside such as in the right picture, pi is a full translation vector and Ti-2Ri-1 is a full transformation matrix).
60% 40%
Hybrid of two canonical structures
Peptide bond geometry
Electronic structure of peptide bond
Peptide bond: planarity
The partially double character of the peptide bond results in
•planarity of peptide groups
•their relatively large dipole moment
Main chain conformation: the , , and angles
The cis (=0o) and trans (=180o) configurations of the peptide group
Skan z wykresem energii
Peptide group: cis-trans isomerization
Because of peptide group planarity, main chain conformation is effectively defined by the and angles.
Side chain conformations: the angles
The dihedral angles with which to describe the geometry of disulfide bridges
Some and pairs are not allowed due to steric overlap (e.g, ==0o)
The Ramachandran map