Multipole analysis on protein charge distribution.

Abstract

The interactions in protein system are known to be very complicated. Extra attention should be paid to special cases where the interactions can be simplified such that the law of physics in proteins can be captured. A literature review on the protein force field was done so as to justify that the dominating guiding force is electrostatic effect. Therefore the focus of this project is on the guiding force in protein-protein / enzyme-substrate interaction.

The popular numerical methods in electrostatic potential calculation were summarized. The simplest calculation of electrostatic potential, i.e. using coulomb’s law of constant linear dielectric, was found to be ambiguous in protein system. Therefore the guiding force problem was tackled from the aspect of the charge distribution of the proteins.

The charge distribution in a protein is very complicated because it consists of thousands atoms bonded together. Multipole moments can provide a good insight to the charge distribution of a protein by giving simple patterns of the charge distribution as seen from a place far away from the protein. However, little study on charge distribution of protein by making use of its multipole moments has been done.

In this project, a programme used to calculate the multipole moments of proteins in both Cartesian and spherical coordinates was developed. It was applied to the study of charge distribution in secondary structures of protein. A simple toy model, ‘Secondary Structure Model’ (SSM), was built so that the charge distribution due to hydrogen bonds can be observed clearly and studied from the multipole moments. Simple patterns in the charge distribution of secondary structure were found in this model.

Besides, enzyme was also studied by calculating its multipoles. Cu-Zn Superoxide dismutase is an enzyme whose catalytic efficiency is found to be enhanced by electrostatic guiding force. Its multipole moments were found to be fluctuating among structures with the same amino acids sequence given in Protein Data Bank. Careful analysis had been done on the reliability of our partial charge parameter (AMBER) by comparing it against the other parameter set, CHARMM. Besides, we also checked on the structure alignment method and multipole calculation programme developed by ourselves. After excluding possible mistakes, we concluded that charged sidechain rotation can cause the fluctuations in multipole moments. This implies that charged sidechain rotation can cause observable charge distribution changes in protein.