Flexibility analysis of biomacromolecules with application to computer-aided drug design

Flexibility characteristics of biomacromolecules can be efficiently determined down to the atomic level by a graph-theoretical technique as implemented in the FIRST (Floppy Inclusion and Rigid Substructure Topology) and ProFlex software packages. The method has been successfully applied to a series of protein and nucleic acid structures. Here, we describe practical guidelines for setting up and performing a flexibility analysis, discuss current bottlenecks of the approach, and provide sample applications as to how this technique can support computer-aided drug design approaches.