Homology modeling is a computational approach to generate three-dimensional structures of protein targets when experimental data about similar proteins are available. Although experimental methods such as X-ray crystallography and nuclear magnetic resonance spectroscopy successfully solved the structures of nearly 150,000 macromolecules, there is still a gap in our structural knowledge. We can fulfill this gap with computational methodologies. Our goal in this chapter is to explain how to perform homology modeling of protein targets for drug development. We choose as a homology modeling tool the program MODELLER. To illustrate its use, we describe how to model the structure of human cyclin-dependent kinase 3 using MODELLER. We explain the modeling procedure of CDK3 apoenzyme and the structure of this enzyme in complex with roscovitine.
Keywords: Cyclin-dependent kinase 3; Drug design; Homology modeling; MODELLER; Molecular recognition.