Back to "Biological Language Modeling Seminar Topics"
Protein Design
- make bR into a soluble protein
- only computational, no experimental validation
- for validation of such an approach, see Mitra, Steitz, Engelman (2002) Pot. Eng 15, 485-492
- review of protein design approaches:
Hecht et al., 1990
Quinn et al., 1994
Munson et la., 1994
Lovejoy et al., 1993
Betz et al., 1995
Choma et al, 1994
Robertson et al., 1994
Bianchi et al., 1994
Schafmeister et al., 1993
- strategy
1. Increase Polar Surface Area to make protein soluble
in membrane proteins: fractional polar surface area of 0.3
in soluble proteins: 0.5-0.6
2. replace non-essential amino acids, but keep essential amino acids [experimentally determined, highly conserved, in contact with retinal, hydrogen bonds, salt bridges, polar residues on surface, Pro, loops]
3. increase contacts between pairs of helices without filling existing cavities in the protein interior
4. increase polar residue number without changing charge balance
5. eliminate amino acids peculiar to membrane proteins, e.g. Trp at helix ends, and Gly
6. remove amphipathicity of helices
7. reinforce good capping sequences at the N- and C0termini of helices
- evaluation
homology modeling
- Amino acid pairwise preference tables
determine pairwise preferences of occurrence for the 20 amino acids near N-cap and C-cap based on DSSP definitions