xin zhancs 882 course project1 study of loop length & residue composition of β-hairpin motif...
TRANSCRIPT
![Page 1: Xin ZhanCS 882 course project1 Study of Loop Length & Residue Composition of β-Hairpin Motif Xin Zhan Nov 27, 2006](https://reader036.vdocuments.mx/reader036/viewer/2022062718/56649eb15503460f94bb6fc8/html5/thumbnails/1.jpg)
Xin Zhan CS 882 course project 1
Study of Loop Length & Residue Composition of
β-Hairpin Motif
Xin Zhan
Nov 27, 2006
![Page 2: Xin ZhanCS 882 course project1 Study of Loop Length & Residue Composition of β-Hairpin Motif Xin Zhan Nov 27, 2006](https://reader036.vdocuments.mx/reader036/viewer/2022062718/56649eb15503460f94bb6fc8/html5/thumbnails/2.jpg)
Xin Zhan CS 882 course project 2
Outline
Research background about β-hairpin motif My task overview Preliminary results Future works
![Page 3: Xin ZhanCS 882 course project1 Study of Loop Length & Residue Composition of β-Hairpin Motif Xin Zhan Nov 27, 2006](https://reader036.vdocuments.mx/reader036/viewer/2022062718/56649eb15503460f94bb6fc8/html5/thumbnails/3.jpg)
Xin Zhan CS 882 course project 3
β-Hairpin Motif Simplest protein motif involving two
beta strands [from Wikipedia] adjacent in primary sequence antiparallel linked by a short loop
As isolated ribbon or part of beta sheet a special case of a turn
direction of protein backbone reverses
flanking secondary structure elements interact (hydrogen bonds)
![Page 4: Xin ZhanCS 882 course project1 Study of Loop Length & Residue Composition of β-Hairpin Motif Xin Zhan Nov 27, 2006](https://reader036.vdocuments.mx/reader036/viewer/2022062718/56649eb15503460f94bb6fc8/html5/thumbnails/4.jpg)
Xin Zhan CS 882 course project 4
Types of Turns β-turn (most common)
donor and acceptor residues of hydrogen bonds are separated by 3 residues (i i +3 H-bonding)
δ-turn i i +1 H-bonding
γ-turn i i +2 H-bonding
α-turn i i +4 H-bonding
π-turn i i +5 H-bonding
ω-loop a longer loop with no internal hydrogen bonding
![Page 5: Xin ZhanCS 882 course project1 Study of Loop Length & Residue Composition of β-Hairpin Motif Xin Zhan Nov 27, 2006](https://reader036.vdocuments.mx/reader036/viewer/2022062718/56649eb15503460f94bb6fc8/html5/thumbnails/5.jpg)
Xin Zhan CS 882 course project 5
Loop Length of β-Hairpin 70% hairpins with
loop length ≤ 7 Most are 2 residues
loops 2 residues loops
prefer type I’ and II’ beta turns
[Sibanda & Thornton 85’]
![Page 6: Xin ZhanCS 882 course project1 Study of Loop Length & Residue Composition of β-Hairpin Motif Xin Zhan Nov 27, 2006](https://reader036.vdocuments.mx/reader036/viewer/2022062718/56649eb15503460f94bb6fc8/html5/thumbnails/6.jpg)
Xin Zhan CS 882 course project 6
Turn Type of Two residue β-Hairpin (1) Types I‘
Residue 1 adopts left-handed alpha-helical conformation
Preference for GLY, ASP, ASN
Residue 2 nearly always GLY
Type II’ Residue 1 only GLY Residue 2 polar amino
acids such as SER, THR
![Page 7: Xin ZhanCS 882 course project1 Study of Loop Length & Residue Composition of β-Hairpin Motif Xin Zhan Nov 27, 2006](https://reader036.vdocuments.mx/reader036/viewer/2022062718/56649eb15503460f94bb6fc8/html5/thumbnails/7.jpg)
Xin Zhan CS 882 course project 7
Turn Type of Two residue β-Hairpin (2)
Residue 2 in type I’ and residue 1 in type II’ has a conformation which can only be adopted by GLY
phi and psi angles are well outside the allowed regions of the Ramachandran plot for amino acids with side chains
![Page 8: Xin ZhanCS 882 course project1 Study of Loop Length & Residue Composition of β-Hairpin Motif Xin Zhan Nov 27, 2006](https://reader036.vdocuments.mx/reader036/viewer/2022062718/56649eb15503460f94bb6fc8/html5/thumbnails/8.jpg)
Xin Zhan CS 882 course project 8
Three Residue β-Hairpin 1st residue
adopts right-handed alpha-helical conformation
2nd in the region between alpha-helix and beta-sheet
3rd position prefer GLY, ASN, ASP
![Page 9: Xin ZhanCS 882 course project1 Study of Loop Length & Residue Composition of β-Hairpin Motif Xin Zhan Nov 27, 2006](https://reader036.vdocuments.mx/reader036/viewer/2022062718/56649eb15503460f94bb6fc8/html5/thumbnails/9.jpg)
Xin Zhan CS 882 course project 9
Four Residue β-Hairpin 1st and 2nd
residues adopting the alpha-helical conformation
3rd in the region between alpha-helix and beta-sheet
4th position prefer GLY, ASN, ASP
![Page 10: Xin ZhanCS 882 course project1 Study of Loop Length & Residue Composition of β-Hairpin Motif Xin Zhan Nov 27, 2006](https://reader036.vdocuments.mx/reader036/viewer/2022062718/56649eb15503460f94bb6fc8/html5/thumbnails/10.jpg)
Xin Zhan CS 882 course project 10
Prediction of Turns [Chou 97’]
Site-independent model based on knowledge that amino acid preferences
at individual positions in ß-turns and does not consider any coupling between the residues in the sequence
1-4 & 2-3 correlation model based on residue coupling
Sequence coupled model based on first-order markov chain involving
conditional probabilities
![Page 11: Xin ZhanCS 882 course project1 Study of Loop Length & Residue Composition of β-Hairpin Motif Xin Zhan Nov 27, 2006](https://reader036.vdocuments.mx/reader036/viewer/2022062718/56649eb15503460f94bb6fc8/html5/thumbnails/11.jpg)
Xin Zhan CS 882 course project 11
β–Hairpin Revisited [Gunasekaran 97’]
A data set of 250 non-homologous proteins For 3 residue loops, major conformational motif is
αR-αR-αL (type I followed by a residue in a left-handed helical conformation)
For 4 residue loops, αR-αR-αR-αL (π-turn motif) Small polar residue ASN, ASP, SER, THR, GLY and
PRO are preferred in loop Identify several CYS-CYS pairs at the non-hydrogen
bonded positions of beta stands
![Page 12: Xin ZhanCS 882 course project1 Study of Loop Length & Residue Composition of β-Hairpin Motif Xin Zhan Nov 27, 2006](https://reader036.vdocuments.mx/reader036/viewer/2022062718/56649eb15503460f94bb6fc8/html5/thumbnails/12.jpg)
Xin Zhan CS 882 course project 12
β–Hairpin Folding Mechanism[Galzitskaya 02’]
Review experimental and theoretical studies of β–hairpin folding mechanism
Hydrogen-bond-centric model Formation of folding droplet starting from beta turn is the
determining factor
Hydrophobic-core-centric model A core structure formed by side chains from both strands
comes first, then brings the two strands together to form hydrogen bonds
![Page 13: Xin ZhanCS 882 course project1 Study of Loop Length & Residue Composition of β-Hairpin Motif Xin Zhan Nov 27, 2006](https://reader036.vdocuments.mx/reader036/viewer/2022062718/56649eb15503460f94bb6fc8/html5/thumbnails/13.jpg)
Xin Zhan CS 882 course project 13
My Task Overview
Extract beta hairpins
Identify loop lengthClassify hairpins based on loop length
Cluster hairpins based on RMSD
1116 proteinsresolution ≤ 1.6 ANon-homologous
Analysis residue preferences
![Page 14: Xin ZhanCS 882 course project1 Study of Loop Length & Residue Composition of β-Hairpin Motif Xin Zhan Nov 27, 2006](https://reader036.vdocuments.mx/reader036/viewer/2022062718/56649eb15503460f94bb6fc8/html5/thumbnails/14.jpg)
Xin Zhan CS 882 course project 14
Distribution of β–Hairpins Based on Loop Length
53
896
336
520 498
296188 164
114 84
0100200300400500600700800900
1000
1 2 3 4 5 6 7 8 9 10
Loop length
Num
ber
of b
eta
hair
pins
![Page 15: Xin ZhanCS 882 course project1 Study of Loop Length & Residue Composition of β-Hairpin Motif Xin Zhan Nov 27, 2006](https://reader036.vdocuments.mx/reader036/viewer/2022062718/56649eb15503460f94bb6fc8/html5/thumbnails/15.jpg)
Xin Zhan CS 882 course project 15
Amino Acids Distributions in Loop Regions The number of a residue i over the total
number of residues in loop regions
0
0.05
0.1
0.15
0.2
0.25
0.3
0.35
ALA ARG ASN ASP GLU GLY LYS PRO SER THR
2 residues loops 4 residues loops 5 residues loops
![Page 16: Xin ZhanCS 882 course project1 Study of Loop Length & Residue Composition of β-Hairpin Motif Xin Zhan Nov 27, 2006](https://reader036.vdocuments.mx/reader036/viewer/2022062718/56649eb15503460f94bb6fc8/html5/thumbnails/16.jpg)
Xin Zhan CS 882 course project 16
A.A. with hydrophilic side A. A. that are in between
![Page 17: Xin ZhanCS 882 course project1 Study of Loop Length & Residue Composition of β-Hairpin Motif Xin Zhan Nov 27, 2006](https://reader036.vdocuments.mx/reader036/viewer/2022062718/56649eb15503460f94bb6fc8/html5/thumbnails/17.jpg)
Xin Zhan CS 882 course project 17
Amino Acids Distributions in 2 Residues Loops
The number of a residue i occurs at position j over the total number of residues at position j.
00.050.1
0.150.2
0.25
0.30.350.4
0.450.5
L1 L2
Rat
io o
f re
sidu
es ASNASPGLYLYSPROSER
![Page 18: Xin ZhanCS 882 course project1 Study of Loop Length & Residue Composition of β-Hairpin Motif Xin Zhan Nov 27, 2006](https://reader036.vdocuments.mx/reader036/viewer/2022062718/56649eb15503460f94bb6fc8/html5/thumbnails/18.jpg)
Xin Zhan CS 882 course project 18
Amino Acid Distributions in 4 Residues Loops
0
0.05
0.1
0.15
0.2
0.25
L1 L2 L3 L4
Rat
io o
f re
sidu
es ASNASPGLUGLYPROSER
![Page 19: Xin ZhanCS 882 course project1 Study of Loop Length & Residue Composition of β-Hairpin Motif Xin Zhan Nov 27, 2006](https://reader036.vdocuments.mx/reader036/viewer/2022062718/56649eb15503460f94bb6fc8/html5/thumbnails/19.jpg)
Xin Zhan CS 882 course project 19
Position Preference of Amino Acids in 5 Residues Loops
A residue’s preference for a loop position
Fij is the number of times residue i occurs in a loop position j
Di is the number of times residue i occurs in the loop region
![Page 20: Xin ZhanCS 882 course project1 Study of Loop Length & Residue Composition of β-Hairpin Motif Xin Zhan Nov 27, 2006](https://reader036.vdocuments.mx/reader036/viewer/2022062718/56649eb15503460f94bb6fc8/html5/thumbnails/20.jpg)
Xin Zhan CS 882 course project 20
Position Preference of Amino Acids in 5 Residues Loops
0
0.5
1
1.5
2
2.5
3
3.5
L1 L2 L3 L4 L5
Pre
fere
nce
ASNASPGLUGLYPROSERTHR
![Page 21: Xin ZhanCS 882 course project1 Study of Loop Length & Residue Composition of β-Hairpin Motif Xin Zhan Nov 27, 2006](https://reader036.vdocuments.mx/reader036/viewer/2022062718/56649eb15503460f94bb6fc8/html5/thumbnails/21.jpg)
Xin Zhan CS 882 course project 21
Considering Structural Similarity
Further cluster beta hairpins based on structural similarity of loop region
Analysis the amino acid distributions in each cluster
![Page 22: Xin ZhanCS 882 course project1 Study of Loop Length & Residue Composition of β-Hairpin Motif Xin Zhan Nov 27, 2006](https://reader036.vdocuments.mx/reader036/viewer/2022062718/56649eb15503460f94bb6fc8/html5/thumbnails/22.jpg)
Xin Zhan CS 882 course project 22
RMSD
Measure the structure similarity between two proteins
Given the position vectors of two sequences of amino acids V, W
![Page 23: Xin ZhanCS 882 course project1 Study of Loop Length & Residue Composition of β-Hairpin Motif Xin Zhan Nov 27, 2006](https://reader036.vdocuments.mx/reader036/viewer/2022062718/56649eb15503460f94bb6fc8/html5/thumbnails/23.jpg)
Xin Zhan CS 882 course project 23
Candidate Clustering Algorithms
Partition methods K-means / Quality Threshold
Hierarchical clustering method UPGMA / Diana
Fuzzy logic based method Fuzzy c-means clustering / Fanny
Neural network based methods SOM / SOTA
![Page 24: Xin ZhanCS 882 course project1 Study of Loop Length & Residue Composition of β-Hairpin Motif Xin Zhan Nov 27, 2006](https://reader036.vdocuments.mx/reader036/viewer/2022062718/56649eb15503460f94bb6fc8/html5/thumbnails/24.jpg)
Xin Zhan CS 882 course project 24
Reference
Sibanda BL, Thornton JM. Beta-hairpin families in globular proteins. Nature 1985. 316(6024):170–174.
Chou, K.C. and Blinn, J.R. Classification and prediction of beta-
turn types. Protein Chem. 1997. 16, 575-595. Gunasekaran K, Ramakrishnan C, Balaram P. Beta-hairpins in
proteins revisited: lessons for de novo design. Protein Eng. 1997 Oct;10(10):1131-41.
Galzitskaya, O. V., J. Higo, and A. V. Finkelstein. 2002. Alpha-helix and beta-hairpin folding from experiment, analytical theory and molecular dynamics simulations. Curr. Protein Pept. Sci.
3:191–200.
![Page 25: Xin ZhanCS 882 course project1 Study of Loop Length & Residue Composition of β-Hairpin Motif Xin Zhan Nov 27, 2006](https://reader036.vdocuments.mx/reader036/viewer/2022062718/56649eb15503460f94bb6fc8/html5/thumbnails/25.jpg)
Xin Zhan CS 882 course project 25
Thank you