protein design based on the designability of protein structures
DESCRIPTION
Protein Design Based on the Designability of Protein Structures. Chen Zeng, PI (GWU) Chao Tang, Co-PI (NEC) Ned Wingreen (Princeton) Naigong Zhang (GWU) Luhua Lai (PKU) NSF Support: DMR-0094176, 0313129. Protein Folds (~1000! Why so small?). Acylphosphatase. Ribosomal protein S6. - PowerPoint PPT PresentationTRANSCRIPT
![Page 1: Protein Design Based on the Designability of Protein Structures](https://reader036.vdocuments.mx/reader036/viewer/2022062422/56812dd3550346895d931b9c/html5/thumbnails/1.jpg)
Protein Design Based on the Designability of Protein Structures
Chen Zeng, PI (GWU)
Chao Tang, Co-PI (NEC)
Ned Wingreen (Princeton)
Naigong Zhang (GWU)
Luhua Lai (PKU)
NSF Support:DMR-0094176, 0313129
![Page 2: Protein Design Based on the Designability of Protein Structures](https://reader036.vdocuments.mx/reader036/viewer/2022062422/56812dd3550346895d931b9c/html5/thumbnails/2.jpg)
Protein Folds (~1000! Why so small?)
Acylphosphatase
Viral DNA-binding domain
Ribosomal protein S6
Ferredoxin
![Page 3: Protein Design Based on the Designability of Protein Structures](https://reader036.vdocuments.mx/reader036/viewer/2022062422/56812dd3550346895d931b9c/html5/thumbnails/3.jpg)
HP Lattice Model
EHH
EHP
EPP
,
( )i j i j
i j
H E r r
2.3
1
0
HH
HP
PP
E
E
E
2HH HP PP
HH PP HP
E E E
E E E
H--Hydrophobic
P--Polar(Dill)
HydrophobicitySegregation
![Page 4: Protein Design Based on the Designability of Protein Structures](https://reader036.vdocuments.mx/reader036/viewer/2022062422/56812dd3550346895d931b9c/html5/thumbnails/4.jpg)
Enumeration (HP Lattice Model) H. Li, C. Tang, N. Wingreen (NEC)
Designability
NS=1
NS=5
NS=0
NS=2
NS=1
95% sequences havedegenerate G-states
Sequences (108) Structures (105)
![Page 5: Protein Design Based on the Designability of Protein Structures](https://reader036.vdocuments.mx/reader036/viewer/2022062422/56812dd3550346895d931b9c/html5/thumbnails/5.jpg)
Top Lattice Structures
![Page 6: Protein Design Based on the Designability of Protein Structures](https://reader036.vdocuments.mx/reader036/viewer/2022062422/56812dd3550346895d931b9c/html5/thumbnails/6.jpg)
…, mm
Off-Lattice m-State ModelPark & Levitt (1995)
![Page 7: Protein Design Based on the Designability of Protein Structures](https://reader036.vdocuments.mx/reader036/viewer/2022062422/56812dd3550346895d931b9c/html5/thumbnails/7.jpg)
Fit to 1PSV By 3-State Model
crms ~ 0.8 Ao
1PSV
![Page 8: Protein Design Based on the Designability of Protein Structures](https://reader036.vdocuments.mx/reader036/viewer/2022062422/56812dd3550346895d931b9c/html5/thumbnails/8.jpg)
Enumeration of Configurations (off-lattice HP model)
ai – accessible surface area of residue i
A= ai < Ac
H = hi a’i (a’i=ai/A)
![Page 9: Protein Design Based on the Designability of Protein Structures](https://reader036.vdocuments.mx/reader036/viewer/2022062422/56812dd3550346895d931b9c/html5/thumbnails/9.jpg)
Searching for New Folds
MAQTDVILCPDTHQKAVCLEKIR EYFDCGLPSAQWCVIKNALLTFRPNMDKILYVVACQGGARASLTLRGAWETRKLHCMQPIVYTTLNGLTMNSAKPLVVTIYSQYNVHLRFDDGFDSKLACVNPMRTYEIWLETFRMLKSPQCNYIAVRIHGRYLDFGSCVNKMYHGFDAALLTRQVLPSLTQIVLTAGNYIGRGPNIPCLDIGSEFIINCAQLVRENHWGVSGLRANLAGTRVNIMPCDEWSILSLMKIHFHDISAQVYTERPQMVKRLAFRATCNMRWDPSIVYTWQFGHLCVHEWMTVINEDSAPILCWHGGLMFGNVVEERPAADIMNWGLRCSLKELTILKNETVGGAPQWYIVHNQFNAKNQKDIETRYPMKSLVSCILHIKMLMKIHYDTFREWQVNSCKLDDVSMSKALLVPQWIVRCSYTPLKWPSTCNMRWDPSIVYTWQFGHLSLVTCAKVINEDSAPILCTRSGLRLTDVNYIPPAADIAQREMRCSLTNQLVDGHETVGGAPQWYFAKRLCRGADEYLIETRYPMKSLILSTAEEKLATDIHYDAGREWQVNSFELITSVETLDLLVPQWIVRCSHTFDIPQS
![Page 10: Protein Design Based on the Designability of Protein Structures](https://reader036.vdocuments.mx/reader036/viewer/2022062422/56812dd3550346895d931b9c/html5/thumbnails/10.jpg)
N=23, r=1.9 A, =0.4 A, 10,000 configurations, 4688 clusters
o o
Histogram of Ns
![Page 11: Protein Design Based on the Designability of Protein Structures](https://reader036.vdocuments.mx/reader036/viewer/2022062422/56812dd3550346895d931b9c/html5/thumbnails/11.jpg)
Energy gap vs. Ns
![Page 12: Protein Design Based on the Designability of Protein Structures](https://reader036.vdocuments.mx/reader036/viewer/2022062422/56812dd3550346895d931b9c/html5/thumbnails/12.jpg)
Design Procedure
II. Pick Top Folds
III. Sequence Design and Verification
I. Model Computation
motif
2nac 2bnh
![Page 13: Protein Design Based on the Designability of Protein Structures](https://reader036.vdocuments.mx/reader036/viewer/2022062422/56812dd3550346895d931b9c/html5/thumbnails/13.jpg)
Design Protocol