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Comparative Study
. 2008 Dec 6;5 Suppl 3(Suppl 3):S207-16.
doi: 10.1098/rsif.2008.0243.focus.

Analysis of polarization in QM/MM modelling of biologically relevant hydrogen bonds

Kittusamy Senthilkumar  1 , Jon I Mujika, Kara E Ranaghan, Frederick R Manby, Adrian J Mulholland, Jeremy N Harvey
Affiliations
Comparative Study

Analysis of polarization in QM/MM modelling of biologically relevant hydrogen bonds

Kittusamy Senthilkumar et al. J R Soc Interface. .

Abstract

Combined quantum mechanics/molecular mechanics (QM/MM) methods are increasingly important for the study of chemical reactions and systems in condensed phases. Here, we have tested the accuracy of a density functional theory-based QM/MM implementation (B3LYP/6-311+G(d,p)/CHARMM27) on a set of biologically relevant interactions by comparison with full QM calculations. Intermolecular charge transfer due to hydrogen bond formation is studied to assess the severity of spurious polarization of QM atoms by MM point charges close to the QM/MM boundary. The changes in total electron density and natural bond orbital atomic charges due to hydrogen bond formation in selected complexes obtained at the QM/MM level are compared with full QM results. It is found that charge leakage from the QM atoms to MM atomic point charges close to the QM/MM boundary is not a serious problem, at least with limited basis sets. The results are encouraging in showing that important properties of key biomolecular interactions can be treated well at the QM/MM level employing good-quality levels of QM theory.

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Figures

Figure 1
Figure 1
Change in electron density upon complex formation calculated at the (i) QM (ΔρQM) and (ii) QM/MM (ΔρQM/MM) levels. (a) Water–N–methylacetamide, (b) formamide–water, (c) imidazole–water, (d) water dimer, (e) imidazole–acetate, (f) acetate–water, (g) protonated methylamine–water, (h) water–imidazole, (i) phenol–water and (j) phenol–imidazole.
Figure 2
Figure 2
Change in electron density upon hydrogen bond formation between guanidinium and acetate fragments, calculated using different basis sets and at the (i) QM (ΔρQM) and (ii) QM/MM (ΔρQM/MM) levels. (a) 6-31G(d), (b) 6-311+G(d,p) and (c) aug-cc-pvtz.
Figure 3
Figure 3
Change in atomic charges (Δq, in atomic units) due to hydrogen bonding: calculated from NBO charges at full QM and QM/MM levels (in brackets). The total charge changes in each fragment (ΣΔq) are also illustrated. (a) Water dimer, (b) formamide–water and (c) guanidinium–acetate.
Figure 4
Figure 4
Change in B3LYP electron density within the acetate ion in the presence of a point charge representation of the guanidinium ion, using the (a) 6-31G(d) and (b) 6-311+G(d,p) basis sets.
Scheme 1
Scheme 1
Schematic representation of the hydrogen bond donor–acceptor complexes optimized by QM/MM methods.
See this image and copyright information in PMC

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