Computational studies of protein sequence and structure
This thesis explores aspects protein function, structure and sequence by computational approaches. A comparative study of definitions of protein secondary structures was performed. Disagreements in assignment resulting from three different algorithms were observed. The causes of inaccuracies in structure assignments were discussed and possibilities of projecting protein secondary structures by different structural descriptors were tested. The investigation of inconsistent assignments of protein secondary structure led to a study of a more specific issue concerning protein structure/function relationships, namely cis/trans isomerisation of a peptide bond. Surveys were carried out at the level of protein molecules to detect the occurrences of the cis peptide bond, and at the level of protein domains to explore the possible biological implications of the occurrences of the structural motif. Research was then focussed on andalpha;-helical integral membrane proteins. A detailed analysis of sequences and putative transmembrane helical structures was conducted on the ABC transporters from different organisms. Interesting relationships between protein sequences, putative a-helical structures and transporter functions were identified. Applications of molecular dynamics simulations to the transmembrane helices of a specific human ABC transporter, cystic flbrosis transmembrane conductance regulator (CFTR), explored some of these relationships at the atomic resolution. Functional and structural implications of individual residues within membrane-spanning helices were revealed by these simulations studies.