Aspects of Protein Structure, Function, and Dynamics in Rational Drug Designing

The availability of the first three-dimensional protein structure of myoglobin, ever since, has changed the way drug designers approach the protein-drug binding problem. Thereafter, the dogma shifted from the “lock and key” to the “induced fit” and later the “conformational selection” model. This shift could be attributed to the various experimental techniques used to solve the protein’s three-dimensional structure and its function. The basis of this new ideology lies in the fact that the atoms of the protein are not static but in constant motion. Furthermore, due to the folding of the protein’s secondary structural elements to arrange themselves spatially, there is a flexibility associated with the whole protein structure. In addition, computational methodologies such as molecular docking and molecular dynamics simulations have proved to be a boon to the drug designing process. This chapter explains, in a nut shell, how protein dynamics and computer-aided drug design play important roles in rational drug designing.