Prediction of protein stability upon point mutations.
Prediction of protein stability upon amino acid substitution is a challenging problem and it will be helpful for designing stable mutants. We have developed a thermodynamic database for proteins and mutants (ProTherm), which has more than 20000 thermodynamic data along with sequence and structure information, experimental conditions and literature information. It is freely accessible at http://gibk26.bse.kyutech.ac.jp/jouhou/protherm/protherm.html. Utilizing the database, we have analysed the relationship between amino acid properties and protein stability and developed different methods, such as average assignment method, distance and torsion potentials and decision tree models to discriminate the stabilizing and destabilizing mutants, and to predict the stability change upon mutation. Our method could distinguish the stabilizing and destabilizing mutants with an accuracy of 82 and 85% respectively from amino acid sequence and protein three-dimensional structure. We obtained the correlation of 0.70 and 0.87, between the experimental and predicted stability changes upon mutations, from sequence and structure respectively. Furthermore, we have developed different web servers for discrimination and prediction and they are freely accessible at http://bioinformatics.myweb.hinet.net/iptree.htm and http://cupsat.tu-bs.de/.
Gromiha
M M
MM
Computational Biology Research Center, National Institute of Advanced Industrial Science and Technology, AIST Tokyo Waterfront Bio-IT Research Building, 2-42 Aomi, Koto-ku, Tokyo 135-0064, Japan. michael-gromiha@aist.go.jp
D000595:Amino Acid Sequence; D030562:Databases, Protein; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D017354:Point Mutation; D011487:Protein Conformation; D011489:Protein Denaturation; D011506:Proteins / Q000737:chemistry* / Q000235:genetics*; D013816:Thermodynamics
D011506:Proteins