Docking carbohydrates to proteins: Empirical free energy functions

Automated docking of small molecules to proteins is a powerful approach for both predicting and understanding the molecular mechanisms of ligand recognition and specificity. Carbohydrate recognition is a key component of many biological processes including innate immunity, metabolism, and immune response. Computational tools specific for studying the molecular basis of carbohydrate recognition have recently been developed that efficiently and accurately dock a flexible carbohydrate to a protein. Two aspects of carbohydrate docking are particularly challenging; parametrization of a the potential energy function for the intra- and intermolecular forces and efficient conformational searching. The combination of a genetic conformational search algorithm coupled with a novel empirically derived free energy function specific for carbohydrates allows the prediction of free energies of formation to 1 kcal-mol(-1). This chapter covers the basic principles of empirical free energy functions and their application to carbohydrates. (c) 2006 American Chemical Society