Ran Yahalom's Page

My Research

Publications:

Thesis:

"Structure Based Prediction of Catalytic Residues":
I developed a structure-based approach to the identification of catalytic residues. The new method is motivated by the difficulty of evolution-based methods to annotate "orphan" Structural Genomics targets, which have very few or no homologs in the databases. My approach is based on the tendency of catalytic residues to be spatially clustered and occluded, on their destabilizing role in the structures and on the differences in catalytic propensity between residue types. These observations were quantified by energy terms and their predictive power augmented by spatial averaging and Z-score transformation. A subset of these energy terms was selected and used to train a support vector machine that discriminates catalytic from non-catalytic residues. Special attention was given to the class imbalance problem which is inherent to the catalytic residue prediction domain and can extremely deteriorate the performance of the SVM. My method showed good performance on a dataset of 34 enzymes that was specifically designed to mimic the Structural Genomics scenario. Each of the proteins in this dataset has a unique CATH fold topology and none were solved with a ligand bound to the active-site. I also tested my method on two datasets that were taken from previous studies. In both cases, results using my method outperformed the reported structure-based results.