The 'pleckstrin homology' (PH) domain is a domain of about 100 residues that occurs in a wide range of proteins involved in intracellular signaling or as constituents of the cytoskeleton. There are several proteins prove to contain PH domains that are separated by other domains or long non-structural sequences. Split PH domains are also found in various proteins, including the second messenger generating enzymes phospholipase C-γ (PLC-γ), the syntrophin scaffold proteins, the Rock1 family Ser/Thr kinases, the actin filament-based molecular motor myosinX, and GTPase-activating protein Centaurin-γ 1. Profile and Hidden Markov Model are currently the most popular primary sequence based method to detect protein domains in protein sequences. In the first part of my thesis, I discuss the poss...[ Read more ]

The 'pleckstrin homology' (PH) domain is a domain of about 100 residues that occurs in a wide range of proteins involved in intracellular signaling or as constituents of the cytoskeleton. There are several proteins prove to contain PH domains that are separated by other domains or long non-structural sequences. Split PH domains are also found in various proteins, including the second messenger generating enzymes phospholipase C-γ (PLC-γ), the syntrophin scaffold proteins, the Rock1 family Ser/Thr kinases, the actin filament-based molecular motor myosinX, and GTPase-activating protein Centaurin-γ 1. Profile and Hidden Markov Model are currently the most popular primary sequence based method to detect protein domains in protein sequences. In the first part of my thesis, I discuss the possible way to extend the PH domain hidden Markov model to fit the usage of this method in detecting split PH domains.

PDZ domains are conserved structural elements of 80 to 100 amino acids that were originally identified in the post-synaptic density protein PSD-95, the Drosophila tumor suppressor discs-large, and the tight-junction protein ZO-1. PDZ domains occur as single or, more frequently, as multiple tandemly repeated copies in a large and diverse set of proteins from all eukaryotes. Rapidly growing number of known PDZ domains and their recognized physiological ligands led to classification problems. Computer programming to remove the redundancies of the PDZ database from SMART will significantly lessen the burden and enhance the efficiency of experiment studies. In the second part, I describe the way to fulfill that.