Quantum Mechanics/Molecular Mechanics (QM/MM) is a multi-scale/multi-resolution computational chemistry method that treats different parts of the systems with different levels of calculations. Using the QM/MM molecular simulation method, Polaris combines the strengths of ab initio QM calculations (accuracy) and MM (speed) approaches. The QM/MM approach was introduced in the 1976 paper of Warshel and Levitt. They, along with Martin Karplus, won the 2013 Nobel Prize in Chemistry for "the development of multiscale models for complex chemical systems".
Polaris uses a fully atomistic simulation, with confirmation of multiple ligands bound to the protein complex, that includes solvent, cofactors and ions to predict binding affinity. The binding affinity is evaluated using the
Taken from: Hatcher Frush, Sekharan, and Keinan, J. Phys. Chem. B 2017, 121, 8142−8148 DOI: 10.1021/acs.jpcb.7b07224