QM/MM Energy Decomposition Using the Interacting Quantum Atoms Approach
Roberto López, Natalia Díaz, E. Francisco, Ángel Martín Pendás, Dimas Suárez
Abstract
The interacting quantum atoms (IQA) method decomposes the quantum mechanical (QM) energy of a molecular system in terms of one- and two-center (atomic) contributions within the context of the quantum theory of atoms in molecules. Here, we demonstrate that IQA, enhanced with molecular mechanics (MM) and Poisson-Boltzmann surface-area (PBSA) solvation methods, is naturally extended to the realm of hybrid QM/MM methodologies, yielding intra- and inter-residue energy terms that characterize all kinds of covalent and noncovalent bonding interactions. To test the robustness of this approach, both metal-water interactions and QM/MM boundary artifacts are characterized in terms of the IQA descriptors derived from QM regions of varying size in Zn(II)- and Mg(II)-water clusters. In addition, we analyze a homologous series of inhibitors in complex with 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 only show the advantages of the IQA QM/MM approach but also address some of the challenges lying ahead for expanding the QM/MM methodology.