title: Can correlated mutations in protein domain families be used for protein design?
abstract: Evidence from diverse studies, such as protein design experiments and analysis of the emergence of drug resistance in human immunodeficiency virus 1 (HIV-1), indicates that protein function can be diminished or altered by mutations at positions distant from the classic 'functional' site. Furthermore, results from correlation analysis of the ligand-binding domain of nuclear receptors suggest that mutation events at positions distributed throughout a protein domain may be involved in functional diversification during the evolution of homologous domain families. This review explores potential applications for a protein design procedure based on correlated substitutions.
authors.affiliation: Department of Biochemistry, University College London, UK. nagl@biochem.ucl.ac.uk
authors.forename: S B
authors.initials: SB
authors.lastname: Nagl
mesh_terms: D019295:Computational Biology; D004352:Drug Resistance, Microbial / Q000235:genetics; D019143:Evolution, Molecular; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008958:Models, Molecular; D009154:Mutation; D015202:Protein Engineering; D017434:Protein Structure, Tertiary / Q000235:genetics*