| This is a master thesis which introduces studies in the field of Molecular Dynamics, and it mainly involves the basics of Molecular Dynamics-molecular force field. Dynamics simulation of biological macromolecular systems currently is an important area of scientific research, such as screening drug molecules and a variety of functional molecules study in biological systems, all of that rely on the semi-empirical force field which can describe the molecular interaction energy accurately. The so-called force field is a set of mathematical formulae describing inter-particle interactions, it needs to determine the expression of these mathematical functions and set the functions’ parameters. Force field is the basics of dynamic simulation, only if interaction is described correctly, can the dynamics process be considered to be valid and accurate, and data analysis based on dynamics simulation to be meaningful[1].After years of development, the accuracy of molecular force field has been greatly improved, but there’s still insufficient, especially in the polarization problem of electrostatic interactions [2]. The so-called polarization, refers to the redistribution of a molecule’s electron density due to an electric field exerted by other molecules(Rick and Stuart2002). While semi-empirical force field uses the method of fixed charge model to describe the electrostatic interactions, when the electrostatic environment in the system has changed dramatically, this method cannot effectively describe changes of the electron density during the whole molecular simulation, which may result in serious mistakes.For more than30years, many attempts have been made to explicitly include polarization effects in molecular modeling[3]. To date, there are several general models that include the polarization effect in the force field such as the fluctuating charge model and induced dipole model, however, one efficient and popular polarizable force field still has not been developed, so the development of an efficient and accurate polarizable force field is still an urgent subject in this field. Especially, considered that protein dynamics simulation take a lot of computer resources, and including polarization effect explicitly in the force field will increase the amount of computation and reduce computational efficiency, so it is necessary to strike a balance between computational speed and accuracy. Our work is moving towards this direction.The EPB model (effective polarizable bond model) developed in our group, allows charges to fluctuate between two oppositely charged atoms of the polar bond, and the fluctuating charges are the sum of permanent (or reference) and induced charges which are determined by the difference of electrostatic potentials at different atoms, broadly speaking, it’s a kind of fluctuating charge model. In this effective polarizable approach, all polar bonds of amino acids are treated as polarizable, and the relevant polarizable parameters were determined by fitting to quantum calculated electrostatic properties of these polar groups. Comparison of the computed hydrogen bond properties and dynamics of proteins with experimental data and with results obtained from the nonpolarizable force field clearly demonstrated that EPB can produce results in much better agreement with experiment, and the present method only adds about5%additional computational time and is therefore highly efficient for practical applications.There will be three chapters in this paper to introduce my research work. First part is the background knowledge, and I will start from the basic framework of this subject, and then extend to the specific field of my research work, introducing its background knowledge and previous studies, particularly, the case of water models will be discussed. In the second part I will introduce how to develop the electrostatic polarization model, and its application in protein force field and protein dynamics simulation. Also I will summarize and have an outlook of this work. For the last part of the paper, I will discuss how to apply the electrostatic polarization model to construct a novel water model and some simulation results of this novel model will be introduced. |
