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Understanding mutations and protein stability through tripeptides
Author(s) -
Anishetty Sharmila,
Anishetty Ramesh,
Pennathur Gautam
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2006.02.079
Subject(s) - pentapeptide repeat , missense mutation , genetics , tripeptide , computational biology , biology , mutation , neutral mutation , protein structure , chemistry , biochemistry , amino acid , peptide , gene
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.