Protein Conformantional Search Using Bees Algorithm

Proteins perform many biological functions in the human body. The structure of the protein determines its function. In order to predict the protein structure computationally, protein must be represented in a proper representation. To this end, an energy function is used to calculate its energy and a conformational search algorithm is used to search the conformational search space to find the lowest free energy corformation

A dihedral angle database of short sub-sequences for protein structure prediction

Protein structure prediction is considered to be the holy grail of bioinformatics. Ab initio and homology modelling are two important groups of methods used in protein structure prediction. Amongst these, ab initio methods assume that no previous knowledge about protein structures is required. On the other hand homology modelling is based on sequence similarity and uses information such as classification, structure, sequence and dihedral angles for prediction.Even though there are many databases for structural and sequence information, there are not many databases for dihedral angles that store all occurring dihedral values of sub-sequences. The existing ones have limitations like not being able to retrieve dihedral values for amino acids of a specific sub-sequence or being designed only for a specific set of proteins based on sequence identity (proteins with < 20% sequence identity). They hence have disadvantages when used in protein structure prediction based on short sub-sequences and exact matches. This paper presents a dihedral angle database for short sub-sequences up to length five. In this database dihedral angles of all proteins were extracted from the Protein Data Bank (PDB) regardless of the percent of sequence similarity. This paper also shows how the database can be used for protein structure prediction using exact matches

On the structure differences of short fragments and amino acids in proteins with and without disulfide bonds

Of the 20 standard amino acids, cysteines are the only amino acids that have a reactive sulphur atom, thus enabling two cysteines to form strong covalent bonds known as disulfide bonds. Even though almost all proteins have cysteines, not all of them have disulfide bonds. Disulfide bonds provide structural stability to proteins and hence are an important constraint in determining the structure of a protein. As a result, disulfide bonds are used to study various protein properties, one of them being protein folding. Protein structure prediction is the problem of predicting the three-dimensional structure of a protein from its one-dimensional amino acid sequence. Ab initio methods are a group of methods that attempt to solve this problem from first principles, using only basic physico-chemical properties of proteins. These methods use structure libraries of short amino acid fragments in the process of predicting the structure of a protein. The protein structures from which these structure libraries are created are not classified in any other way apart from being non-redundant. In this thesis, we investigate the structural dissimilarities of short amino acid fragments when occurring in proteins with disulfide bonds and when occurring in those proteins without disulfide bonds. We are interested in this because, as mentioned earlier, the protein structures from which the structure libraries of ab initio methods are created, are not classified in any form. This means that any significant structural difference in amino acids and short fragments when occurring in proteins with and without disulfide bonds would remain unnoticed as these structure libraries have both fragments from proteins with disulfide bonds and without disulfide bonds together. Our investigation of structural dissimilarities of amino acids and short fragments is done in four phases. In phase one, by statistically analysing the phi and psi backbone dihedral angle distributions we show that these fragments have significantly different structures in terms of dihedral angles when occurring in proteins with and without disulfide bonds. In phase two, using directional statistics we investigate how structurally different are the 20 different amino acids and the short fragments when occurring in proteins with and without disulfide bonds. In phase three of our work, we investigate the differences in secondary structure preference of the 20 amino acids in proteins with and without disulfide bonds. In phase four, we further investigate and show that there are significant differences within the same secondary structure region of amino acids when they occur in proteins with and without disulfide bonds. Finally, we present the design and implementation details of a dihedral angle and secondary structure database of short amino acid fragments (DASSD) that is publicly available. Thus, in this thesis we show previously unknown significant structure differences in terms of backbone dihedral angles and secondary structures in amino acids and short fragments when they occur in proteins with and without disulfide bonds