Grafting of protein-protein binding sites |
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Authors: | Shide Liang Lan Xiao Fenglou Mao Lin Jiang Yuzhen Han Luhua Lai |
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Institution: | (1) Institute of Physical Chemistry, Peking University, 100871 Beijing, China |
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Abstract: | A strategy for grafting protein-protein binding sites is described. Firstly, key interaction residues at the interface of
ligand protein to be grafted are identified and suitable positions in scaffold protein for grafting these key residues are
sought. Secondly, the scaffold proteins are superposed onto the ligand protein based on the corresponding Cα and Cβ atoms. The complementarity between the scaffold protein and the receptor protein is evaluated and only matches with high
score are accepted. The relative position between scaffold and receptor proteins is adjusted so that the interface has a reasonable
packing density. Then the scaffold protein is mutated to corresponding residues in ligand protein at each candidate position.
And the residues having bad steric contacts with the receptor proteins, or buried charged residues not involved in the formation
of any salt bridge are mutated. Finally, the mutated scaffold protein in complex with receptor protein is co-minimized by
Charmm. In addition, we deduce a scoring function to evaluate the affinity between mutated scaffold protein and receptor protein
by statistical analysis of rigid binding data sets. |
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Keywords: | grafting superposing geometric complementarity scoring function protein engineering |
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