Protein Design Based on the Designability of Protein Structures

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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

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Protein Folds (1000! Why so small?)
Acylphosphatase
Ribosomal protein S6
Viral DNA-binding domain
Ferredoxin
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HP Lattice Model
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Enumeration (HP Lattice Model) H. Li, C. Tang,
N. Wingreen (NEC)
95 sequences have degenerate G-states
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Top Lattice Structures
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Off-Lattice m-State Model Park Levitt (1995)
(f,y) (f1,y1), (f2,y2), , (fm,ym)
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Fit to 1PSV By 3-State Model
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Enumeration of Configurations
(off-lattice HP model)
ai accessible surface area of residue i
AS ai lt Ac
H S hi ai
(aiai/A)
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Searching for New Folds
MAQTDVILCPDTHQKAVCLEKIR EYFDCGLPSAQWCVIKNALLTFR P
NMDKILYVVACQGGARASLTLR GAWETRKLHCMQPIVYTTLNGLT MNS
AKPLVVTIYSQYNVHLRFDD GFDSKLACVNPMRTYEIWLETFR MLKSP
QCNYIAVRIHGRYLDFGS CVNKMYHGFDAALLTRQVLPSLT QIVLTAG
NYIGRGPNIPCLDIGS EFIINCAQLVRENHWGVSGLRAN LAGTRVNIM
PCDEWSILSLMKIH FHDISAQVYTERPQMVKRLAFRA TCNMRWDPSIV
YTWQFGHLCVHE WMTVINEDSAPILCWHGGLMFGN VVEERPAADIMNW
GLRCSLKELT ILKNETVGGAPQWYIVHNQFNAK NQKDIETRYPMKSLV
SCILHIKM LMKIHYDTFREWQVNSCKLDDVS MSKALLVPQWIVRCSYT
PLKWPS TCNMRWDPSIVYTWQFGHLSLVT CAKVINEDSAPILCTRSGL
RLTD VNYIPPAADIAQREMRCSLTNQL VDGHETVGGAPQWYFAKRLCR
GA DEYLIETRYPMKSLILSTAEEKL ATDIHYDAGREWQVNSFELITSV
ETLDLLVPQWIVRCSHTFDIPQS
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Histogram of Ns
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Energy gap vs. Ns
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Design Procedure
I. Model Computation
III. Sequence Design and Verification
bab motif
2bnh
2nac
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Design Protocol