| DOT User's Guide |
Version 1.0alpha |
Released 12/17/1998 |
The basic DOT calculation requires an electrostatic potential field and a description of the excluded volume for the still molecule, a set of coordinates and a charge model for the moving molecule, and a list of relative orientations of the still and moving molecules for which the interaction energies are to be evaluated. It is also necessary to decide what size grid should be used in the calculation.
There are a variety of utilities included with DOT to aid in the preparation of this data. The starting point is a pair of coordinate files in PDB format. The electrostatic properties of all atoms, residues, and ligands must be known or estimated. This is normally not as formidable as it sounds, since the calculation is dominated by the obvious fully charged groups, but occasionally this step is difficult. It is in fact the same procedure that must be followed to prepare a file for molecular dynamics calculations or for electrostatic analysis, so a wide range of tools are available. This manual describes the combined use of the Molecular Simulations InsightII program and the University of Houston Brownian Dynamics (UHBD) program, as these are the tools currently used in our own laboratory. Similar tools exist for Charmm, AMBER, and GROMOS, to name only a few. Several utility commands are provided with DOT to aid in the manipulation of hydrogen atoms.
The choice of grid is usually straightforward. The spacing between grid points should be no larger than 1 Angstrom. The span of the grid should be such that, when the still molecule is centered on the grid, there is room for the moving molecule on all sides in all orientations. This is necessary because the FFT method used by DOT is inherently periodic. Portions of the moving molecule which fall outside the grid boundaries "wrap around" and enter the grid on the opposite face. If the wrapped portion of the moving molecule comes too close to the still molecule, it will either collide or generate spurious interactions. For most purposes, a cubic grid 128 Angstroms on a side is satisfactory.
If N is the number of grid divisions per spatial dimension (128 in our examples), the cost of the calculation is proportional to M log M, where M = N3, so a large value of N can be expensive.