Search for identical octapeptides in unrelated proteins: Structural plasticity revisited

Abstract

Since proteins are dynamic in nature, they can alter their local structure in response to changes in their environment factors such as temperature, pH, phosphorylation, and binding of other small molecules. These conformational changes are extremely important for the correct folding and functioning of proteins. There are also a number of diseases associated with protein conformational change such as amyloid diseases. To stimulate research into the above factors which specify one conformation over another, different theoretical models have been proposed and tested against sequence similar distant structure protein fragments. In order to simplify the computational complexity of identifying conformational changes in proteins, various local sequence search algorithms were employed and the structural plasticity in unrelated proteins was examined by various research groups. In the present work, we revisit the mechanism of structural plasticity in unrelated proteins with increased number of structures in Protein Data Bank by comparing identical octapeptides in unrelated proteins with dictionary of protein secondary structure extracted from existing experimental data. Our goal is to bring out the influence of hydrophobic residues, hydrophilic residues, flanking residues, difference in secondary structural propensities of surrounding residues, difference in phi-psi angles and local and nonlocal interactions in identical octapeptides adopting different conformations. Also we have used surrounding hydrophobicity, environment dependent interaction energy, atomic mean force potential, structural unit contacts and difference profiles models to explore the factors which cause structural plasticity. The results discussed here may provide insights into protein folding, design and function.

Performance of secondary structure prediction methods on proteins containing structurally ambivalent sequence fragments

“…GOR method uses the information of the eight flanking residues (i.e., j + 8 and j − 8, where j is the central residue for which secondary structural state to be predicted) to predict the structural states, and therefore, the residues contributing for long‐range cooperative interactions is missing in the algorithm. This implies that the conformation change phenomenon of identical octapeptides in different proteins is due to the cooperative long‐range interactions . Interestingly, no obvious correlation coefficient has been observed between JPred and other prediction methods, and this is due to the incorporation of optimized version of JNET algorithm, which makes use of results obtained from several prediction methods and thus makes the prediction from the JPred server more unique and accurate than other methods.…”

“…In our previous work, we have searched for identical fragments in unrelated Protein Data Bank sequences. From our search, we have found 52 structurally ambivalent heptapeptides and 30 structurally ambivalent octapeptide pairs with different secondary structures, which form the source of our study.…”

Pairwise contact energy statistical potentials can help to find probability of point mutations

“…The residues coming around a central residue are assigned with their pairwise residue contact energy from Table obtained from the procedure described above and their sum represents the pairwise interaction energy of the central residue. The sum of pairwise interaction energy of all the residues in a protein is computed . The difference of sum of pairwise interaction energy ( E diff ) of wildtype protein ( E wt ) and each point mutant ( E mut ) is computed.…”

Search and Analysis of Identical Reverse Octapeptides in Unrelated Proteins

“…In our previous work [15], we compiled 3124 non-redundant protein sequences and their corresponding three state secondary structure assignments from PDB [16] to perform various computational studies. The protein sequences in the dataset were reversed by using a string reverse algorithm with an in house PERL program.…”

“…The importance of cooperative long-range interactions for protein stability was further verified experimentally by studying the fragments of chymotrypsin inhibitor 2 in barley [14]. In our previous paper, we have characterized 30 identical octapeptides adopting different conformations by computing difference in the number of long-range contacts of residues [15].…”