The understanding of binding interactions between any protein and a small molecule plays a key role in the rationalization of affinity and selectivity. It is essential for an efficient structure-based drug design (SBDD) process. FMO enables ab initio approaches to be applied to systems that conventional quantum-mechanical (QM) methods would find challenging. The key advantage of the Fragment Molecular Orbital Method (FMO) is that it can reveal atomistic details about the individual contributions and chemical nature of each residue and water molecule toward ligand binding which would otherwise be difficult to detect without using QM methods. In this chapter, we demonstrate the typical use of FMO to analyze 19 crystal structures of β1 and β2 adrenergic receptors with their corresponding agonists and antagonists.
Keywords: CADD; Chemical interactions; Computer-Aided Drug Design; Drugs; FMO; Fragment Molecular Orbitals method; GAMESS; GPCR G-protein-coupled receptors; General Atomic and Molecular Electronic Structure System; Modeling; PIEDA; Pair Interaction Energies Decomposition Analysis; Pair-interaction energy; QM; Quantum Mechanics; Receptor; SBDD; Structure Based Drug Design.