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Use of conserved key amino acid positions to morph protein folds
Author(s) -
Reddy Boojala V. B.,
Li Wilfred W.,
Bourne Philip E.
Publication year - 2002
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.10152
Subject(s) - protein data bank (rcsb pdb) , protein engineering , protein data bank , computational biology , mutant , protein structure , protein structure prediction , fold (higher order function) , sequence (biology) , amino acid , peptide sequence , protein secondary structure , amino acid residue , chemistry , sequence alignment , protein design , conserved sequence , protein sequencing , mutation , biology , biochemistry , computer science , gene , enzyme , programming language
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. © 2002 Wiley Periodicals, Inc. Biopolymers 64: 139–145, 2002