title: Helical ambivalency induced by point mutations.
abstract: BACKGROUND
  Mutation of amino acid sequences in a protein may have diverse effects on its structure and function. Point mutations of even a single amino acid residue in the helices of the non-redundant database may lead to sequentially identical peptides which adopt different secondary structures in different proteins. However, various physico-chemical factors which govern the formation of these ambivalent helices generated by point mutations of a sequence are not clearly known.
  
  
  RESULTS
  Sequences generated by point mutations of helices are mapped on to their non-helical counterparts in the SCOP database. The results show that short helices are prone to transform into non-helical conformations upon point mutations. Mutation of amino acid residues by helix breakers preferentially yield non-helical conformations, while mutation with residues of intermediate helix propensity display least preferences for non-helical conformations. Differences in the solvent accessibility of the mutating/mutated residues are found to be a major criteria for these sequences to conform to non-helical conformations. Even with minimal differences in the amino acid distributions of the sequences flanking the helical and non-helical conformations, helix-flanking sequences are found be more solvent accessible.
  
  
  CONCLUSIONS
  All types of mutations from helical to non-helical conformations are investigated. The primary factors attributing such changes in conformation can be: i) type/propensity of the mutating and mutant residues ii) solvent accessibility of the residue at the mutation site iii) context/environment dependence of the flanking sequences. The results from the present study may be used to design de novo proteins via point mutations.
authors.affiliation: Department of Chemistry, University of Delhi, Delhi, India.
authors.forename: Nicholus
authors.initials: N
authors.lastname: Bhattacharjee
authors.forename: Parbati
authors.initials: P
authors.lastname: Biswas
mesh_terms: D030562:Databases, Protein; D017354:Point Mutation; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012997:Solvents / Q000737:chemistry
chemical_list: D011506:Proteins; D012997:Solvents