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.
Anishetty
Sharmila
S
Centre for Biotechnology, Anna University, Chennai 600 025, India.
Anishetty
Ramesh
R
Pennathur
Gautam
G
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