title: Use of conserved key amino acid positions to morph protein folds.
abstract: By using three-dimensional (3D) structure alignments and a previously published method to determine Conserved Key Amino Acid Positions (CKAAPs) we propose a theoretical method to design mutations that can be used to morph the protein folds. The original Paracelsus challenge, met by several groups, called for the engineering of a stable but different structure by modifying less than 50% of the amino acid residues. We have used the sequences from the Protein Data Bank (PDB) identifiers 1ROP, and 2CRO, which were previously used in the Paracelsus challenge by those groups, and suggest mutation to CKAAPs to morph the protein fold. The total number of mutations suggested is less than 40% of the starting sequence theoretically improving the challenge results. From secondary structure prediction experiments of the proposed mutant sequence structures, we observe that each of the suggested mutant protein sequences likely folds to a different, non-native potentially stable target structure. These results are an early indicator that analyses using structure alignments leading to CKAAPs of a given structure are of value in protein engineering experiments.
authors.affiliation: San Diego Supercomputer Center, University of California-San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
authors.forename: Boojala V B
authors.initials: BV
authors.lastname: Reddy
authors.forename: Wilfred W
authors.initials: WW
authors.lastname: Li
authors.forename: Philip E
authors.initials: PE
authors.lastname: Bourne
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D019992:Databases as Topic; D008969:Molecular Sequence Data; D009154:Mutation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017386:Sequence Homology, Amino Acid
chemical_list: D000596:Amino Acids