The Research Of Calculating System Charge Via Partition-iterative Quantum Method

Molecular force field uses empirical potential function to describe the interactions between nuclei in the system.Based on molecular force field molecular dynamics simulation plays an important role in the research of dynamic behavior of biological macromolecules.In the molecular force field,non-bond interaction is usually considered being composed of Van Der Waals interaction and electrostatic interaction,and the fixed point charge potential of Kulun is used to calculate the electrostatic interaction.The advantage of this method is the high computational efficiency.But in some cases,it can not describe the electrostatic properties accurately such as polarization effect and anisotropy of electron cloud distribution.We can get a more accurate result by using quantum chemistry calculation and Population Analysis to calculate the charges of specific conformation.However,the computation time will increases rapidly when the atomic number increases.It is difficult to apply this method to the biological system with large molecular.So it is necessary to propose a method to calculate the atomic charges in the system and to reflect system structure.In this paper,an iterative strategy based on system partition and quantitative calculation to the sub-system is developed.It is applied to calculate atomic charges of different conformations in macromolecular systems.We designate it the Partition-Iterate Quantum(PIQ)method.In this method,the system is divided into several fragments,and one fragment is chosen as the target molecule.The atomic charges of other molecular fragments are used as background charge.The target atomic charges can be obtained by high precision quantum chemistry calculation.Next,the target molecules in the system are reselected.And the atomic charges,which are got from precisely Quantum calculation,are applied as the background charge.The atomic charges of the target molecule are calculated.And so forth,when the atomic charges of all the molecular fragments in the molecular system do not change,the iterative calculation is completed.The atomic charges of the system are obtained by counting the atomic charges of all the molecular fragments in the system.In this paper,the PIQ method is applied to the complex system that composed of two components which choosing from amino acid,nucleic acid,water molecule and ion.The accuracy and computational efficiency of the method are discussed by comparing with those obtained by direct quantitative results of complete system.The PIQ method can obtain atomic charges which are similar to the results obtained by direct quantitative calculation certain the system with specific ions and this method improves efficiency.We also study the influence of different initialization modes of atomic charge on the convergence of PIQ method.For the systems that do not contain ions,the order of convergent efficiency of different initialization methods is: quantification calculation of molecular fragments without background charge,atomic charges in CHARMM molecular force field,charge assigned randomly.But in the system containing ions,the convergence of PIQ method of the three charge initialization methods are approximately the same.In summary,The PIQ method can be used to calculate the atomic charge of biological macromolecules efficiently and accurately.This method can be applied to the field like force field development,the calculation of electrostatic properties and virtual screening and so on.