title: Kinetic computational alanine scanning: application to p53 oligomerization.
abstract: We have developed a novel computational alanine scanning approach that involves analysis of ensemble unfolding kinetics at high temperature to identify residues that are critical for the stability of a given protein. This approach has been applied to dimerization of the oligomerization domain (residues 326-355) of tumor suppressor p53. As validated by experimental results, our approach has reasonable success in identifying deleterious mutations, including mutations that have been linked to cancer. We discuss a method for determining the effect of mutations on the location of the dimerization transition state.
authors.affiliation: Department of Chemistry, Stanford University, Stanford, CA 94305-5447, USA.
authors.forename: Lillian T
authors.initials: LT
authors.lastname: Chong
authors.forename: William C
authors.initials: WC
authors.lastname: Swope
authors.forename: Jed W
authors.initials: JW
authors.lastname: Pitera
authors.forename: Vijay S
authors.initials: VS
authors.lastname: Pande
mesh_terms: D000409:Alanine / Q000235:genetics*; D019943:Amino Acid Substitution / Q000235:genetics*; D019295:Computational Biology / Q000379:methods; D003198:Computer Simulation; D019281:Dimerization; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D017510:Protein Folding; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D016159:Tumor Suppressor Protein p53; D000409:Alanine