Application of semi-empirical quantum mechanical methods in estimation of biomolecular interactions

Despite considerable progress in computational methods for calculating interactions between small molecules and proteins, estimation of the geometry of protein-ligand complexes and their binding free energies remains as a challenging task in the structure-based drug design. For an accurate description of these interactions requires the inclusion of quantum mechanical contributions using an extended atomic orbital basis set. For this purpose, some semi-empirical quantum mechanical methods have been developed that are much less expensive than more accurate “ab initio” and “density functional theory” methods.Currently, the application of fast and efficient semi-empirical quantum mechanical methods for calculating electronic properties of large molecules and biological systems becomes a routine task. In this contribution, the development of these methods and their successful applications in different fields – especially in biomolecular interactions – are reviewed.