Visualisation in the SPROUT molecular design program.

Abstract

SPROUT is an interactive computer system for structure based molecular design. The system consists of several modules that address the different subproblems of structure based drug design. This paper describes the visualisation techniques applied in the program: the display of the novel (geometric region) representation of the interaction sites and the molecular surface display based on a 3D grid representation of the cavity. The hydrogen bonding regions are represented by set operations (subtraction and intersection) of simple spherical and conical 3D objects (with given radii and opening angle) Some complex hydrogen bonding regions are represented by intersections of six or more basic objects. A method for calculating a triangular mesh representation (with normal vectors) of the analytical surfaces of the objects, that have sharp edges and corners because of the intersections, is presented in the paper. The geometric parameters of the interaction regions can be changed interactively in which case the surface display is updated real-time. The volume of space that is available for ligand generation (the cavity of the receptor site) is represented on a 3D grid within SPROUT. The surface of the available space is visualised using an algorithm presented in the paper, that generates a polygonial mesh of the grid points. The grid is also used to cut out stericaly forbidden parts of the interaction site regions. The surface of the reduced object is also visualised using further sphere subtractions. The presented algorithms are fast, aplicable in interactive visualisation programs. Result images of the rendering of the surfaces, calculated by the algorithms, are demonstrated on examples taken from applications of SPROUT to practical ligand design problems.