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Predicting folding free energy changes upon single point mutations
- Source :
- Bioinformatics. 28:664-671
- Publication Year :
- 2012
- Publisher :
- Oxford University Press (OUP), 2012.
-
Abstract
- Motivation: The folding free energy is an important characteristic of proteins stability and is directly related to protein's wild-type function. The changes of protein's stability due to naturally occurring mutations, missense mutations, are typically causing diseases. Single point mutations made in vitro are frequently used to assess the contribution of given amino acid to the stability of the protein. In both cases, it is desirable to predict the change of the folding free energy upon single point mutations in order to either provide insights of the molecular mechanism of the change or to design new experimental studies. Results: We report an approach that predicts the free energy change upon single point mutation by utilizing the 3D structure of the wild-type protein. It is based on variation of the molecular mechanics Generalized Born (MMGB) method, scaled with optimized parameters (sMMGB) and utilizing specific model of unfolded state. The corresponding mutations are built in silico and the predictions are tested against large dataset of 1109 mutations with experimentally measured changes of the folding free energy. Benchmarking resulted in root mean square deviation = 1.78 kcal/mol and slope of the linear regression fit between the experimental data and the calculations was 1.04. The sMMGB is compared with other leading methods of predicting folding free energy changes upon single mutations and results discussed with respect to various parameters. Availability: All the pdb files we used in this article can be downloaded from http://compbio.clemson.edu/downloadDir/mentaldisorders/sMMGB_pdb.rar Contact: ealexov@clemson.edu Supplementary information: Supplementary data are available at Bioinformatics online.
- Subjects :
- Statistics and Probability
Protein Folding
In silico
Mutation, Missense
Protein Data Bank (RCSB PDB)
medicine.disease_cause
Biochemistry
symbols.namesake
medicine
Humans
Point Mutation
Molecular Biology
Root-mean-square deviation
Genetics
Physics
Mutation
Protein Stability
Point mutation
Proteins
Original Papers
Computer Science Applications
Gibbs free energy
Folding (chemistry)
Computational Mathematics
Computational Theory and Mathematics
symbols
Thermodynamics
Protein folding
sense organs
Biological system
Software
Subjects
Details
- ISSN :
- 13674811 and 13674803
- Volume :
- 28
- Database :
- OpenAIRE
- Journal :
- Bioinformatics
- Accession number :
- edsair.doi.dedup.....1e76c045ccf1b4c4b8e270e57e848a9a