CYP1A1 and CYP1A2 exhibit catalytic activity predominantly for the 2-hydroxylation of estradiol, whereas CYP1B1 exhibits catalytic activity predominantly for 4-hydroxylation of estradiol. To understand why CYP1B1 predominantly hydroxylates the 4-position of estradiol, we constructed three-dimensional structures of CYP1A1 and CYP1B1 by homology modeling, using the crystal structure of CYP1A2, an...

Enzymes are one of the most important groups of drug targets, and identifying possible ligand-enzyme interactions is of major importance in many drug discovery processes. Novel computational methods have been developed that can apply the information from the increasing number of resolved and available ligand-enzyme complexes to model new unknown interactions and therefore contribute to answer o...

In this chapter, we explore means for predicting protein residues that interact with small molecules. We will motivate the problem by describing potential uses for such information and proceed to discuss methods advanced for prediction. We describe our sequence-based approach and contrast it with another current methodwhich relies on predicted protein structure to help identify ligand-binding r...

The growing interest in the identification of kinase inhibitors, promising therapeutics in the treatment of many diseases, has created a demand for the structural characterization of the entire human kinome. At the outset of the drug development process, the lead-finding stage, approaches that enrich the screening library with bioactive compounds are needed. Here, protein structure based method...

The evolution of our physics-based computational methods for determining protein conformation without the introduction of secondary-structure predictions, homology modeling, threading, or fragment coupling is described. Initial use of a hard-sphere potential captured much of the structural properties of polypeptide chains, and subsequent more refined force fields, together with efficient method...

Efforts to develop effective antibody therapeutics are frequently hampered by issues such as aggregation and nonspecificity, often only detected in late stages of the development process. In this study, we used a high throughput cross-reactivity assay to select nonspecific clones from a naïve human repertoire scFv library displayed on the surface of yeast. Most antibody families were de-enriche...