ABSTRACT
The goal of conformational analysis is to shed light on conformational characteristics of flexible biomolecules and to gain insight into the relationship between their flexibility and their function. Because of the importance of this approach, conformational analysis plays a role in many computational projects ranging from computer-aided drug design to the analysis of molecular dynamics simulations and protein folding. In fact, most structurebased drug design projects today use conformational analysis techniques as part of their toolchest. As will be discussed in Chapter 16, in structure-based drug design a rational effort is applied to identifying potential drug molecules that bind favorably into a known three-dimensional (3D) binding site [1], the structure of which was determined through X-ray crystallography, NMR spectroscopy, or computer modeling. Because such an effort requires, among other things, structural compatibility between the drug candidate and the binding site, computational methods were developed to ‘‘dock’’ ligands into binding sites [2]. These docking calculations are used for screening large virtual molecular libraries, saving both time and money. However, although docking is fairly straightforward with rigid molecules, it becomes significantly more complicated when flexible molecules are considered. This is because flexible molecules can adopt many different conformations, each of which may, in principle, lead to successful docking.
