Diffusion accessibility as a method for visualizing macromolecular surface geometry

Abstract

Important three-dimensional spatial features such as depth and surface concavity can be difficult to convey clearly in the context of two-dimensional images. In the area of macromolecular visualization, the computer graphics technique of ray-tracing can be helpful, but further techniques for emphasizing surface concavity can give clearer perceptions of depth. The notion of diffusion accessibility is well-suited for emphasizing such features of macromolecular surfaces, but a method for calculating diffusion accessibility has not been made widely available. Here we make available a web-based platform that performs the necessary calculation by solving the Laplace equation for steady state diffusion, and produces scripts for visualization that emphasize surface depth by coloring according to diffusion accessibility. The URL is http://services.mbi.ucla.edu/DiffAcc/.

Keywords: Laplace; Poisson-Boltzmann; binding sites; computer graphics; protein surfaces; surface curvature.

Figure 1

Visualization of the diffusion accessibility for three example proteins with concave features. For each protein, a standard ray-traced rendering of the molecule is shown on the left with protein subunits colored individually. The middle and right views illustrate the diffusion accessibility using two different methods for coloring. (middle) A three-part color spectrum (magenta-white-green) is applied to the diffusion accessibility values; low diffusion accessibility is magenta. (right) Darker shading is applied to regions of low diffusion accessibility, reserving individual color hues for separate protein chains. In the right panels, the bound polypeptide or ligand is rendered in stick form and colored by atom type (magenta=carbon) in order to show the correspondence between the binding cleft and the regions of low diffusion accessibility. Note that the diffusion accessibility is for the protein surface in the absence of bound peptide or ligand. (top) The structure of the peptide-binding domain of the major histocompatibility complex (MHC) (PDB ID: 1HSA22). (middle) The structure of the HIV protease dimer (PDB ID: 2AID23). (bottom) The structure of the erythropoietin (Epo) receptor dimer (PDB ID: 1EBP24). All images were produced using the program PyMol.