Applying Molecular Electrostatic Potential To The Computation Of Intermolecular Electrostatic Interaction Energy

The calculation of intermolecular interactions is an important part of the study of catalysis,materials,drug design and biological processes.The electrostatic interaction energy is the main part of the intermolecular interaction.The calculation of electrostatic interaction energy of biological macromolecules is mostly carried out under the classical framework of molecular mechanics,using the Coulomb's law and relying on the point charges of two atoms involved in the interaction.The atomic charge is an approximate expression of the spatial distribution of the electron cloud,which contains a large approximation,mainly to approximate the movement of electrons in space to a point.Thus the atomic charge will import errors.For this reason,the method of returning the atomic charge to the spatial distribution is theoretically considered to improve the calculation of the electrostatic interaction energy,such as the polarization charge method.This article replaces the atomic charge with the molecular electrostatic potential of the protein and compares the difference between the two results.The main research contents of this article are as follows:(1)Comparing the molecular electrostatic potential and electrostatic interaction energy under HF method and B3 LYP method.The objects of the study are the water dimers,the benzene dimers and the acetylene dimers.The difference between the two methods is small.Under the same premise of calculating the basis set,the partial and overall differences in the molecular electrostatic potential obtained under the two methods are small enough.Thus,the HF method was used to calculate the electrostatic potential and electrostatic energy of the protein-ligand complex.(2)The choice of the rational base group.In order to calculate the electrostatic potential of the protein from the 6-311++G** series and the cc-pVnZ series,a peptide chain was selected as the test protein.The electrostatic potential of the protein was calculated at the level of HF/6-311G**,HF/6-311++G**,HF/6-311++G(2df,2pd),HF/cc-pVDZ,HF/cc-pVTZ and HF/cc-pVQZ respectively.The results show that it is reasonable and accurate to calculate molecular electrostatic potential and electrostatic energy at HF/cc-pVTZ level.(3)Comparing molecular electrostatic potential and electrostatic energy with HF/cc-p VTZ level and the Coulomb's law.We use the water dimer,the benzene dimer and the acetylene dimer as the research objects,and compare the electrostatic energy of the dimer molecules obtained by the two methods.The results show that for small molecules,the results obtained under the two methods are not significantly different.(4)The electrostatic potential and electrostatic energy of protein-ligand complexes were compared at HF/cc-pVTZ level and the Coulomb's law.We selected 10 rational protein-ligand complexes as the objects of the study,then compared and analyzed the electrostatic energy of the dimer molecules obtained by the two methods.The results show that the results obtained under the two methods are different significantly.Therefore,it is proposed that the calculation of the electrostatic energy of the biomacromolecule needs to be improved from the point charge method to the electrostatic potential method.(5)Under the HF/cc-pVTZ level and the Coulomb's law,the amino acids were intercepted from 7 ? to 10 ? from the ligand molecule,and the electrostatic potential and electrostatic energy between ligand molecules were calculated.The results show that under the same calculation method,the difference in electrostatic energy between amino acids and ligand at different distances is not significantly different.