The polarizable dipole–dipole interaction model was formulated in our laboratory to rapidly simulate hydrogen bonding in biosystems. In this paper, this model is improved and further parametrized for stacking, T-shaped, and X–H···π interactions by adding the orbital overlap term and fitting to 19 CCSD(T)/CBS interaction energy curves of training dimers. The performance of our model is assessed through its application to more than 100 complexes, including hydrogen-bonded, stacked, T-shaped, and X–H···π complexes. For 124 relatively small testing complexes, our model reproduces benchmark equilibrium intermolecular distances with a root-mean-square deviation (RMSD) of 0.08 Å, and it reproduces benchmark interaction energies with a 0.64 kcal/mol RMSD. For 14 large noncovalent complexes, our model reproduces benchmark equilibrium intermolecular distances with a RMSD of 0.05 Å, and it reproduces benchmark interaction energies with a 0.80 kcal/mol RMSD. Extensive comparisons are made to interaction energies calculated via the M06-2X and M06-2X-D3 methods, via the well-known nonpolarizable AMBER99 force field method, via the popular polarizable AMOEBA force field method, and via semiempirical quantum mechanical (SQM) methods. Our statistical evaluations show that our model outperforms the AMBER99, AMOEBA, and SQM methods and is as accurate as the M06-2X and M06-2X-D3 methods. In summary, the model developed in this work is reasonable, and the newly introduced orbital overlap term is effective in the accurate modeling of the noncovalent interactions. Our testing results also indicate that the polarization interaction term is important in the evaluation of hydrogen bonding, whereas the orbital overlap is important in examining short hydrogen bonding, T-shaped, and X–H···π interactions. Our model may serve as a new tool for modeling biological systems where hydrogen bonding, stacking, T-shaped, and X–H···π interactions are of general importance.

In this paper, the polarizable dipole-dipole interaction model was further developed via adding lone-pair dipole moment treatment for nucleobase adenine, cytosine, and guanine. Not only polar covalent bonds, such as C=O, C―O, N―H, C―H and O―H were regarded as bond dipoles, but also nitrogens with lone-pair electrons of adenine, cytosine, and guanine were regarded as lone-pair dipoles. The parameters needed were first determined by treating model complexes. The model was subsequently applied to a series of nucleobase- and nucleoside-containing hydrogen-bonded complexes to rapidly predict the equilibrium hydrogen bond distances and the intermolecular inte-raction energies. It was observed that the model developed in this work reproduce the MP2/6-31+G(d,p) and B3LYP/6-31+G(d,p) equilibrium hydrogen bond distances with a root mean square error of less than 0.004 nm and the counterpoise-corrected MP2/aug-cc-pVTZ intermolecular interaction energies with a root mean square error of less than 2.93 kJ/mol, which was also highly efficient, demonstrating that the model developed in this work was rea-sonable and useful.

The polarizable dipole–dipole interaction model, which explicitly involves the permanent dipole–dipole interaction, the van der Waals interaction, the polarization contribution and the covalency interaction, has been proposed in our lab for N–H⋯OC and C–H⋯OC hydrogen-bonded complexes containing amides and peptides. In this paper, the polarizable dipole–dipole interaction model is further developed and applied to hydrogen-bonded complexes containing ribose, deoxyribose, fructose, glucose, maltose and sucrose. We regard the chemical bonds O–H, C–H and C–O in ribose, deoxyribose, fructose, glucose, maltose and sucrose molecules as bond dipoles. The magnitude of the bond dipole moment varies according to its environment. The parameters needed are first determined from the training dimers. The polarizable dipole–dipole interaction model is then applied to a series of carbohydrate-containing hydrogen-bonded complexes. The calculation results show that the polarizable dipole–dipole interaction model not only can produce the equilibrium hydrogen bond distances compared favorably with those produced by the MP2/6-31+G(d,p) method and can produce the interaction energies in good agreement with those yielded by the high quality counterpoised-corrected MP2/aug-cc-pVTZ method, but is much more efficient as well, demonstrating that the polarizable dipole–dipole interaction model and the parameters determined are reasonable and useful.

The binding energies of thirty-six hydrogen-bonded peptide-base complexes, including the peptide backbone-ase complexes and amino acid side chain-base complexes, are evaluated using the analytic potential energy function established in our lab recently and compared with those obtained from MP2, AMBER99, OPLSAA/L, and CHARMM27 calculations. The comparison indicates that the analytic potential energy function yields the binding energies for these complexes as reasonable as MP2 does, much better than the force fields do. The individual N-H…O=C, N-H…N, C-H…O=C, and C-H…N attractive interaction energies and C=O…O=C, N-H…H-N, C-H…H-N, and C-H…H-C repulsive interaction energies, which cannot be easily obtained from ab initio calculations, are calculated using the dipole-dipole interaction term of the analytic potential energy function. The individual N-H…O=C, C-H…O=C, C-H…N attractive interactions are about −5.3±1.8, −1.2±0.4, and −0.8 kcal/mol, respectively, the individual N-H…N could be as strong as aboutt -8.1 kcal/mol or as weak as −1.0 kcal/mol, while the individual C=O…O=C, N-H…H-N, C-H…H-N, and C-H…H-C repulsive interactions are about 1.8±1.1, 1.7±0.6, 0.6±0.3, and 0.35±0.15 kcal/mol. These data are helpful for the rational design of new strategies for molecular recognition or supramolecular assemblies.

Understanding the mechanisms underlying the assembly of nucleobases is a great challenge. The ability to deeply understand how nucleobases interact with themselves as well as with other molecules will allow us to gain valuable insights into how we might be able to harness these interesting biological molecules to construct complex nanostructures and materials. Uracil and thymine derivatives have been reported for use in biological applications and in self-assembling triple hydrogen bonded systems. Either uracil or thymine possesses three binding sites (Site 1, Site 2, and Site 3) that can induce strong directional N-H…O=C hydrogen bonding interaction. In this paper, theoretical calculations are carried out on the structural features and binding energies of hydrogen-bonded dimers and trimers formed by uracil and thymine bases. We find that the hydrogen bonds formed through Site 1 are the strongest, those formed through Site 3 are next, while those formed through Site 2 are the weakest. The atoms in molecules analysis show that the electron densities at the bond critical points and the corresponding Laplacians have greater values for those hydrogen bonds formed through Site 1 than through Site 2. All these results indicate that a uracil (or thymine) would interact with another uracil or thymine most likely through Site 1 and least likely through Site 2. We also find that a simple summation rule roughly exists for the binding energies in these dimers and trimers.

The individual hydrogen bonding energies in N-methylacetamide chains were evaluated at the MP2/6-31+G** level including BSSE correction and at the B3LYP/6-311++G(3df,2pd) level including BSSE and van der Waals correction. The calculation results indicate that compared with MP2 results, B3LYP calculations without van der Waals correction underestimate the individual hydrogen bonding energies about 5.4 kJ mol−1 for both the terminal and central hydrogen bonds, whereas B3LYP calculations with van der Waals correction produce almost the same individual hydrogen bonding energies as MP2 does for those terminal hydrogen bonds, but still underestimate the individual hydrogen bonding energies about 2.5 kJ mol−1 for the hydrogen bonds near the center. Our calculation results show that the individual hydrogen bonding energy becomes more negative (more attractive) as the chain becomes longer and that the hydrogen bonds close to the interior of the chain are stronger than those near the ends. The weakest individual hydrogen bonding energy is about −29.0 kJ mol−1 found in the dimer, whereas with the growth of the N-methylacetamide chain the individual hydrogen bonding energy was estimated to be as large as −62.5 kJ mol−1 found in the N-methylacetamide decamer, showing that there is a significant hydrogen bond cooperative effect in N-methylacetamide chains. The natural bond orbital analysis indicates that a stronger hydrogen bond corresponds to a larger positive charge for the H atom and a larger negative charge for the O atom in the N-H⋯O=C bond, corresponds to a stronger second-order stabilization energy between the oxygen lone pair and the N-H antibonding orbital, and corresponds to more charge transfer between the hydrogen bonded donor and acceptor molecules.

A new method is proposed to quick predict the strength of intermolecular hydrogen bonds. The method is employed to produce the hydrogen-bonding potential energy curves of twenty-nine hydrogen-bonded dimers. The calculation results show that the hydrogen-bonding potential energy curves obtained from this method are in good agreement with those obtained from MP2/6-31+G** calculations by including the BSSE correction, which demonstrate that the method proposed in this work can be used to calculate the hydrogen-bonding interactions in peptides.

In this paper, B3LYP and MP2 methods are used to investigate the binding energy of seventeen antiparallel and parallel β-sheet models. The results indicate that the binding energy obtained from B3LYP calculations is weaker than that obtained from MP2 calculations but the relative binding energy yielded by B3LYP is almost the same as that by MP2. For the antiparallel β-sheets in which two N-H⋯O=C hydrogen bonds can form either a large hydrogen-bonded ring or a small hydrogen-bonded ring, the binding energy increases obviously when one large ring unit is added, whereas it only changes slightly when one small ring unit is added because of the secondary electrostatic repulsive interaction existing in the small ring unit which is estimated to be about 20 kJ/mol. For the parallel β-sheet models, the binding energy increases almost exactly linearly with the increase of the chain length.