Application of computational sequence and structure analysis to the description of protein function.

摘要

Genome sequencing projects are producing large amounts of linear amino acid sequences. More than 2,000,000 protein sequences have been described. The challenge of the post-genomic era is to understand the biochemical functions and biological roles of these proteins. In this context, computational approaches to the analysis of protein sequences and structures have become highly relevant. In each of the three chapters of my thesis, I present one such computational approach that covers the analysis of protein sequences, the prediction of protein structure from sequence, and the derivation of phenotypic information from sequence and structure information. Specifically the thesis is divided into the following chapters:; Chapter 1. Multivariate analysis of multiple sequence alignments. This chapter deals with the development of a fully automatic sequence-based analysis for functional residue detection and sequence classification.; Chapter 2. Comparative modeling of potassium inward rectifier channels. This chapter deals with the modeling of the three-dimensional cytoplasmic structure of potassium channels to achieve complete structural coverage of the family, and with the comparison of the electrostatic potentials derived from the models using a novel image-based method.; Chapter 3. Sequence and structure-based analysis of Fabry disease mutations. This chapter deals with the identification of features derived from the sequence and structure of alpha-galactosidase that allow for the prediction of the phenotype of Fabry disease related mutations.