QM/MM Energy Decomposition Using the Interacting Quantum Atoms Approach

The interacting quantum atoms (IQA) method decom-poses the quantum mechanical (QM) energy of a molecular system interms of one- and two-center (atomic) contributions within the contextof the quantum theory of atoms in molecules. Here, we demonstrate thatIQA, enhanced with molecular mechanics (MM) and Poisson-Boltzmann surface-area (PBSA) solvation methods, is naturally extendedto the realm of hybrid QM/MM methodologies, yielding intra- andinter-residue energy terms that characterize all kinds of covalent andnoncovalent bonding interactions. To test the robustness of thisapproach, both metal-water interactions and QM/MM boundaryartifacts are characterized in terms of the IQA descriptors derivedfrom QM regions of varying size in Zn(II)-and Mg(II)-water clusters.In addition, we analyze a homologous series of inhibitors in complexwith a matrix metalloproteinase (MMP-12) by carrying out QM/MM-PBSA calculations on their crystallographic structures followed by IQA energy decomposition. Overall, these applications not onlyshow the advantages of the IQA QM/MM approach but also address some of the challenges lying ahead for expanding the QM/MMmethodology

Automated summary

The interacting quantum atoms (IQA) method allows for the decomposition of the quantum mechanical (QM) energy of a molecular system using the quantum theory of atoms in molecules framework. This method, enhanced with molecular mechanics (MM) and Poisson-Boltzmann surface-area (PBSA) solvation methods, can be extended to hybrid QM/MM methodologies. The IQA QM/MM approach has been demonstrated to successfully characterize metal-water interactions and QM/MM boundary artifacts, as well as describe covalent and noncovalent bonding interactions.