Finding and filling protein cavities using cellular logic operations

Anatomy of protein pockets and cavities: Measurement of binding site geometry and implications for ligand design

“…For example, several methods place dots on the surface of atoms at a distance equal to the van der Waals plus probe radii, and surface components are then derived from the collection of these dots (Shrake & Rupley, 1973;Rashin et al, 1986). Alternatively, a volume box containing the protein is divided into cubic grids, and the collection of the grid points that lie outside any atom is processed for identification and quantification of cavities and pockets (Voorintholt et al, 1989;Ho & Marshall, 1990;Delaney, 1992;Kleywegt & Jones, 1994). In general, the quality of such measurement of pocket volume and area depends on the level of spacing, because a count of the number of dots/grids is the basis of the measurement.…”

“…Research toward this end includes analytical area and volume calculation (Connolly, 1983;Richmond, 1984;Gibson & Scheraga, 1987); cavity identification and measurement (Rashin et al, 1986;Voorintholt et al, 1989;Ho & Marshall, 1990;Alard & Wodak, 1991;Nicholls et al, 1993;Smart et al, 1993;Hubbard et al, 1994;Kleywegt & Jones, 1994;Williams et al, 1994); pocket or cleft computation (Kuntz et al, 1982;Delaney, 1992;Levitt & Banaszak, 1992;Laskowski, 1995;Peters et al, 1996); and molecular shape representation (Lin et al, 1994). Although useful, their application to pocket calculations is limited by lack of fully automatic computations, lack of analytical measurements of area and volume with real physical meaning, and/or use of arbitrarily adjusted parameters.…”

Detection, delineation, measurement and display of cavities in macromolecular structures

“…This program contains tools for expanding and contracting masks as well as for logically combining pairs of masks ('AND', 'OR' etc.) which enable emulation of Delaney's cavitydetection methods (Delaney, 1992).…”

“…Additionally, if the cavity is in touch with the outside world, a distance constraint has to be used in order to prevent the cavity from 'spilling out' into the great wide open. Delaney (1992) uses so-called cellular logic techniques derived from image processing (namely, expansion and contraction of a 3D 'image') in order to detect and delineate cavities in a protein structure which has been mapped onto a 3D logical grid. This approach is very elegant in that it provides a way of visualizing cavities which are not closed off from the outside world (i.e.…”

A Connected Set Algorithm for the Identification of Spatially Contiguous Regions in Crystallographic Envelopes

“…For example, cavities in proteins can be viewed as spatially contiguous regions of unoccupied points after projection of the electron density of the protein atoms onto an appropriate three-dimensional grid (Delaney, 1992;Kleywegt & Jones, 1994b).…”