Understanding mutations and protein stability through tripeptides.
A novel methodology to predict the local conformational changes in a protein as a consequence of missense mutations is proposed. A pentapeptide at the locus of mutation plays the dominant role and it is analyzed in terms of tripeptides. A measure for spatial and temporal fluctuations in a pentapeptide is devised and validated. The method does not involve any prior knowledge of structural templates from sequence homology studies. Structural deformations can be predicted with about 70-80% reliability in any protein. Disease causing mutations and benign mutations have been addressed. In particular, p53, retinoblastoma protein and lipoprotein lipase are studied in detail.
Centre for Biotechnology, Anna University, Chennai 600 025, India.
Sharmila
S
Anishetty
Ramesh
R
Anishetty
Gautam
G
Pennathur
D020816:Amino Acid Motifs; D003430:Cross-Sectional Studies; D018360:Crystallography, X-Ray; D030562:Databases, Protein; D006801:Humans; D020125:Mutation, Missense / Q000235:genetics*; D010455:Peptides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011487:Protein Conformation; D013816:Thermodynamics; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry
D010455:Peptides; D016159:Tumor Suppressor Protein p53