C-1-13
Estimation of Non-covalent Interactions witha New Efficient Dispersion Corrected HF Approach
Tatsusada Yoshida 1, *, Akira Mashima 1 , Katsunori Sasahara 1 ,Yuto Shibata 1 , Masahiro Eguchi 1 , Seiji Hitaoka 2 , and Hiroshi Chuman 1*tyoshida@tokushima-u.ac.jp
1

Graduate School of Pharmaceutical Sciences, The University of Tokushima, 1-78-1 Shomachi, Tokushima770-8505, Japan
2
Institute for Materials Chemistry and Engineering and International Research Center for Molecular System,
Kyushu University, Fukuoka 819-0395, Japan

Keywords: BSSE, Dispersion, Hartree–Fock, LERE

[1] T. Yoshida, Y. Munei, S. Hitaoka, H. Chuman. J. Chem. Inf. Model., 2010, 50, 850–860.

M06-2X/6-31+G(d)B3LYP-D2/6-31+G(d)B2PLYP-D/6-31+G(d)MP2/6-31+G(d)HF-D/6-31+G(d)HF/6-31+G(d)MAE (kcal/mol)

An accurate estimation of binding interaction energy associated with complex formation of aligand and protein is important for understanding the binding mechanism and rational drug design.
Although the dispersion is one of the most important interaction as well as hydrogen-bonding andelectrostatic ones, its evaluation based on molecular orbital methods is still not easy task. In thisstudy, we examined our newly proposed dispersion correction for the Hartree–Fock method (HF-D)
on several complexes of biologically relevant molecules.
We selected a set of eighteen small non-covalently bonded complexes: six dispersion-dominated(DISP), nine hydrogen-bonded (HB), and three other types of complexes (others). The geometry ofeach complex was fully optimized at the MP2/6-311++G(d,p) level. In our HF-D approach, the HF
energy was corrected by introducing damped empirical dispersion energy term (f(R)C 6 /R 6 ) using asigmoid-type function. We calculated interaction energies using HF-D and the counterpoisecorrections were employed to reduce the basis set superposition errors (BSSE). The performanceof HF-D were confirmed by comparing with post-HF methods (CCSD(T) and MP2) and several
DFT based methods (M06-2X and Grimme’s dispersion corrected B3LYP-D2 and B2PLYP-D).
Figure 1 shows the mean absolute error (MAE) of2.5
interactionenergies
estimatedfromtheDISP (n = 6)
CCSD(T)/aug-cc-pVTZ reference values. The overall
HB (n = 9)
2.0
performance of HF-D is excellent; as expected, HF-Dothers (n = 3)
more accurately reproduces interaction energies foroverall (n = 18)
all three types of complexes than the conventional HF
1.5
method. It should be noted that MAE of HF-D shows
significantly smaller than that of more expensive MP2
1.0
in all complexes (MAE(overall) = 0.40 and 1.01
kcal/mol, respectively). Although M06-2X gives thebest performance (MAE(overall) = 0.30) among the0.5
tested methods, HF-D is competitive with the M06-2X
and other dispersion corrected B3LYP-D2 and0.0
B2PLYP-D. HF-D approach is probably effective andpractical, compared with time-consuming post-HF
and DFT methods to quantitatively evaluate theinteraction energy of large molecular systems such ascomplex of a ligand with protein. We will also discussthebinding
mechanismofaseriesofbenzenesulfonamides with carbonic anhydrase using Figure 1. Comparison of the performance ofLERE-QSAR procedure [1] in which HF-D approach HF-D and other methods for non-covalently
is introduced for estimation of binding interaction bonded complexes.
energy.