Probing the range of applicability of structure‐ and energy‐adjustedQM/MMlink bondsII: Optimized link bond parameters for density functional tight binding approaches

Abstract

Optimized link bond parameters for the CαCβ bond of 22 different capped amino acid model systems have been determined at SCC DFTB/mio (self‐consistent charge density functional tight‐binding), SCC DFTB/3ob and GFNn‐xTB (n = 0, 1, and 2) level in conjunction with the AMBER 99SB, 14SB, and 19B force fields. The resulting parameter sets have been compared to newly calculated reference data obtained via resolution‐of‐identity 2nd order Møller–Plesset perturbation theory. The data collected in this work suggests that the optimized values in this study provide a more suitable setup of the QM/MM link bonds compared to the use of a single global setting applied to every amino acid fragmented by the QM/MM interface. The results also imply that a transfer of the ideal link bond settings between different levels of theory is not advised. In contrast, virtually identical parameters were obtained in calculations employing different variants of the AMBER force field. Considering the increasing success of tight binding based approaches being inter alia a results of their exceptional accuracy/effort ratio the provided collection of link atoms parameters provides a valuable resource for QM/MM studies of biomacromolecular systems as demonstrated in an exemplary QM/MM MD simulation of the β‐amyloid/Zn2+ complex.

Probing the range of applicability of structure‐ and energy‐adjusted QM/MM link bonds III: QM/MM MD simulations of solid‐state systems at the example of layered carbon structures

“…Similar problems resulting from an inadequate placement of the link atoms have also been observed in a QM/MM MD simulation of the Zn-binding site of the β-amyloid system reported earlier. 26 The resulting energies over the simulation time (total simulation time of 25 ps, time step of 2.0 fs) are depicted in Figure 7 indicating the wrong ratios, differing AE0.1 from the ideal value, cause a deviation of the energy of about 10 kcal/mol (too small) and 20 kcal/mol (too large). In addition, the geometry is also affected, leading to either a different bulging motive of the defect in case of the smaller ratio or no bulging at all when using the larger ratio.…”

“…To enable interactions between QM and MM zone capping hydrogen atoms (covalently bound to the carbon atoms near the MM region, which would be forming covalent bonds to carbon atoms in the MM region) were set up as hydrogen link atoms. To achieve an accurate description of the link bonds, the location of the capping hydrogen atom was derived from the respective parent bond as described in previous works 22,26 :…”

“…22 The employment of semi-empirical methods 23,24 such as the density functional tight binding (DFTB) method 25 was also combined successfully with force fields as described in previously published works. [26][27][28][29][30] A particular advantage of the good accuracy/effort ratio of DFTB methods is the fact that comparably large systems can be treated for long simulation times as for instance recently demonstrated in a QM/MM MD simulation of Li and Na intercalation in graphite. 31 In this case a 2d periodic QM/MM setup was applied, containing two layers of the graphitic surface (576 carbon atoms, 2304 valence electrons).…”

Challenges in Protein QM/MM Simulations with Intra-Backbone Link Atoms

“…Generally, when considering residues of enzyme catalytic and binding sites, only their sidechains are put in a QM subsystem. This way, hydrogen link atoms along Cα–Cβ bonds are the most common enzymological setup, and it also enjoys the most developed methodology with a number of studies conducted to fine-tune its performance. , …”