Fleshing-out pharmacophores with volume rendering of molecular charge densities and hyperwall visualization technology


Preston J. MacDougall, Department of Chemistry, Middle Tennessee State University, 1301 E. Main St., Murfreesboro, TN 37132 and Christopher E. Henze, Data Analysis Group, NASA Ames Research Center, MS T27A, Moffett Field, CA 94035.
Pharmacophores are an important consideration in the drug discovery process, particularly during computational screening of molecular libraries. Typically, these key elements are represented by little more than a type-label and coordinates. We present images of pharmacophores generated by interactive, and parallel, computational “screening” of molecular libraries on a 7x7 hyperwall. We utilize volume rendering of the Laplacian of the total charge density computed for a homologous series of antibiotic compounds (penicillin derivatives and peptido-mimetic drug candidates). The rendering is done interactively so as to optimally image characteristic features of multiple pharmacophores within a single molecule. The rendering is also done in parallel, so that corresponding pharmacophores in related drug molecules can be visually compared and contrasted in exquisite detail. The hyperwall has seven rows of seven high-resolution monitors, and associated processors, networked synchronously. Each column of screens on the hyperwall corresponds to one type of pharmacophore in the drug molecules, while the rows of screens on the hyperwall correspond to different drug molecules in the homologous series. The technical requirements for this powerful visualization technique will be outlined, and its potential contribution to the drug discovery process will be discussed.