Design of reduced point charge models for proteins

In previous work, we developed an approach to locate extrema in smoothed promolecular electron density (ED) and molecular charge density (CD) field ρscalculated through the Poisson equation.

In this formalism, the smoothed analytical CD distribution function of an atom ρa,s(r) is obtained from its atomic charge qaand the Poisson equation.

To follow the pattern of local maxima and minima in a ED or CD scalar field, as a function of the degree of smoothing, the following strategy was adopted. First, each atom of a molecule is considered as a starting point. As the smoothing degree increases, each point moves along a path to reach a location where the ED or CD gradient value vanishes. Convergence of trajectories leads to a reduction of the number of points.

The approach is applied to the design of amino acid (AA) reduced point charge models (Figure). Full protein reduced point charge descriptions are generated through a superposition algorithm of the AA templates onto the protein structure.

The charges and interaction parameters were first implemented in TINKER and, later, in GROMACS to carry out molecular dynamics simulations of proteins. Various models and implementation schemes are now tested for the Ubiquitin system and are discussed based on thermodynamical, structural, and dynamical results.