Investigating the sequence patterns in the secondary structure of proteins

The Anfinson experiments performed in the 1950s to understand the principles of protein folding, suggested that the primary amino acid sequence contains the information that specifies the folded native structure. Two dimensional NMR hydrogen exchange, coupled with stopped flow pulse labeling experiments showed that the folding intermediates usually possess the same secondary structure as that of the native protein. This evidence supports the argument that formation of secondary structure largely depends on the local amino acid sequence since the intermediate folding states presumably do not have the established tertiary contacts of the native structure. Since then, researchers have been trying to understand the factors that influence the stability of secondary structures such as alpha helix, beta sheets and loops. Experiments towards understanding the helix propensity of different amino acids have been carried out in a number of studies using peptide and protein models. The results of the peptide models were generally comparable to those of the studies done by using protein models.; In contrast to the helix propensity studies, the propensities of beta sheet formation have been limited and more complicated. To understand more about the stability of beta strands, the sequence patterns of proteins in relation to beta strands was studied in this thesis. A unique parameter called the 'Neighbor Dependent propensity' was included to study the sequence patterns in beta strands. The 'Neighbor Dependent propensity' calculated the effect of neighboring amino acid type on the propensity of residues for adopting a particular secondary structure. Experiments were designed using GB1 protein as a model, to study the influence of neighboring amino acid to form beta strand.; Some unique sequence patterns have emerged from this study. Previous studies showed His and Leu residues as moderate beta strand formers, but by incorporating 'Neighbor Dependent propensity', it was shown that His and Leu residues are among the best beta strand formers in a leucine environment. Thr residue was considered a best beta strand former and Gly residue a moderate beta strand former by previous studies. But our studies indicate that it is a moderate beta strand former and Gly a worst beta strand former when leucine residues are its neighbors. Thus, by incorporating 'Neighbor Dependent propensity', it was shown that neighboring amino acids influence on the propensity of a residue to adopt a particular secondary structure.