MOZYME is a semiempirical quantum chemistry method that is particularly useful for studying large molecular systems, including protein-ligand interactions. it is based on the Localized Molecular Orbital (LMO) method, which allows for the efficient modeling of large systems by focusing on local interactions within the system. This method is particularly advantageous for studying proteins and sections of DNA, where the size of the system can make traditional quantum mechanical methods computationally prohibitive. The MOZYME method has been applied to study the interactions between ligands and proteins by enabling the semiempirical mod-eling of these large complexes. It uses a divide-and-conquer approach, dividing the system into smaller subsystems, which significantly speeds up the computational process. It can be integrated with other computational methods to enhance its capabilities. For example, it has been combined with Density Functional Theory (DFT) to study the pKa values of ionizable residues in proteins, providing a more comprehensive understanding of protein-ligand interactions. One of the key advantages of MOZYME is its linearscaling SCF method, which allows systems of up to 15,000 atoms to be modeled. This makes it particularly suitable for studying protein-ligand interactions, where the size and complexity of the system can otherwise limit the applicability of quantum mechanical methods. The MOZYME method is implement in the MOPAC software .