A major shortcoming of semiempirical (SE) molecular orbital methods is their severe underestimation of molecular polarizability compared with experimental and _ab initio_ (AI) benchmark data…
In combined quantum mechanical and molecular mechanical (QM/MM) free energy simulations, how to synthesize the accuracy of ab initio (AI) QM/MM (AI/MM) methods with the speed of semiempirical QM/MM (SE/MM) methods remains a challenge…