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Fragmentation Methods: Bridging the Gap between Quantum Chemistry and Large Systems

Xiao HE
East China Normal University

Routine quantum mechanical (QM) calculation on macromolecules is still a formidable task in computational chemistry and biology. The major computational limitation of QM methods is the scaling problem, since the cost of ab initio calculation scales n-th power or even worse with the system size. In the past decade, the fragmentation approach based on the chemical locality has become one of the central focuses in developing linear-scaling QM method for large systems. The attractive aspect of fragmentation approach is that it can be highly parallelized on massive computer nodes and also applied to all levels of ab initio electronic structure theories with a minimum of development efforts. 
In my talk, two fragmentation methods and their applications to macromolecules will be discussed. They are the electrostatically embedded generalized molecular fractionation with conjugate caps (EE-GMFCC) method and automated fragmentation quantum mechanics/molecular mechanics (AF-QM/MM) approach. The EE-GMFCC method is developed from the MFCC approach, which was initially aimed to obtain accurate protein-ligand QM interaction energy. By introducing the electrostatic embedding field in each fragment calculation and two-body interaction energy correction on top of the MFCC approach, the EE-GMFCC method is capable of accurately reproducing the QM molecular properties (such as the dipole moment, electron density and electrostatic potential), total energy and electrostatic solvation energy from full system calculations for proteins.
On the other hand, the AF-QM/MM was aimed for efficient QM calculation of protein NMR parameters including chemical shift, chemical shift anisotropy tensor and spin-spin coupling constant. In the AF-QM/MM approach, each amino acid and all the residues in its vicinity are automatically assigned as the QM region through a distance cutoff for each residue-centric QM/MM calculation. Local chemical properties of central residue can be obtained from individual QM/MM calculation. The AF-QM/MM approach precisely reproduces the NMR chemical shifts of proteins in gas phase from full system QM calculations. Furthermore, by incorporating implicit and explicit solvent models, the protein NMR chemical shifts calculated by the AF-QM/MM method are in excellent agreement with experimental values. The applications of the AF-QM/MM method may also be extended to more general biological systems such as DNA/RNA and protein-ligand complexes.