Improved Polarizable Dipole-dipole Interaction Model For Hydrogen Bonding,Stacking,T-shaped And X-H…? Interactions

Noncovalent interactions such as hydrogen bonding,stacking,T-shaped,and X-H…?interactions are known to play key roles in determining the structures,properties,and functions of biomolecules.The ability to accurately and efficiently simulate these noncovalent interactions is critical for the computer simulation of biological processes.The polarizable dipole-dipole interaction model has been formulated in our laboratory to rapidly estimate the strength of hydrogen bonds in complexes.In this work,this model is further developed to rapidly simulate not only hydrogen bonding but also stacking,T-shaped and X-H…? interactions.The main contents of this thesis are listed as follows:1.Based on the understanding of charge transfer in noncovalent interactions,the polarizable dipole-dipole interaction model was revised by re-expressing the orbital overlap term(Eorb)as a function of the overlapping integral between the nonbonding orbital nlp of the proton acceptor and the X-H antibonding orbital ? of the proton donor.This improved model was parameterized by fitting to CCSD(T)/CBS interaction energies of 24 training dimers,including 10 hydrogen-bonded dimers,4 stacked dimers,4 T-shaped dimers,6 X-H…? and other dimers.2.This improved model with the parameters optimized in this thesis was then applied to evaluate 139 noncovalent complexes,including 36 hydrogen-bonded complexes,32 stacked complexes,41 T-shaped complexes,30 X-H…? and other complexes.The results were directly compared to the benchmark CCSD(T)/CBS interaction energies collected from the literatures.The statistical evaluations show that this model reproduces the benchmark CCSD(T)/CBS interaction energies with the RMSD of 0.92,0.50,0.52 and 0.27 kcal/mol for hydrogen-bonded,stacked,T-shaped,X-H…? and other complexes,respectively.3.With respect to the high quality CCSD(T)/CBS results published in the literatures,extensive comparisons were made to the interaction energies calculated via the M06-2X and M06-2X-D3 density functional theory methods,the AMBER99 nonpolarizable force field method,the AMOEBA polarizable force field method and the 15 semiempirical quantum mechanical(SQM)methods.Our statistical evaluations demonstrate that this model outperforms the AMBER99,AMOEBA,SQM methods,and our results are as accurate as that from the M06-2X and M06-2X-D3 methods.The aforementioned information further illustrates that the improved model is reasonable.4.This model was further tested to calculate the interaction energies for 14 larger literature-available biological or non-bio logical noncovalent complexes.The results indicate that this model reproduces the benchmark interaction energies with a 0.80 kcal/mol RMSD,and outperforms not only the AMBER99 and AMOEBA force field methods but also the M06-2X and M06-2X-D3 methods.5.The computational efficiency of this model was also analyzed.The comparisons show that the calculation speed of this revised polarizable dipole-dipole interaction model is four orders of magnitude faster than that of the well-known M06-2X and M06-2X-D3 methods.The results presented in this thesis prove that this model is efficient,the calculation precision of this model is at least equal to M06-2X and M06-2X-D3 methods,and outperforms the AMBER99,AMOEBA and SQM methods.We expect the model developed in this work will serve as a new tool for biological process simulations.