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rebump

Daniel Gschwend

Overview

In difficult or fussy systems, improved results can be obtained by allowing orientations to get closer to the receptor with the aim that minimization will salvage them. Normally, orientations with such close contacts would be thrown out, but by decreasing the allowable contact distance to atoms comprising the active site we permit minimization to attempt to recover them. This is easily achieved by recreating the bump grid generated by chemgrid with reduced polar and non-polar contact distances for active site surface atoms only (a "Swiss-cheese" effect is observed when all atoms are given reduced contacts, so the ligand atoms may fill holes created in the interior of the receptor resulting in energetically unsalvagable orientations). This is also referred to as "softening" the active site. Note that the reduced distances apply only in determining which orientations will be minimized, not in the actual energy calculation. Many more orientations will pass the bump filter, so run-times will increase, often significantly. However, result quality can be dramatically improved. A particular positive aspect of this method is that the dependence of result quality on the number of bumps is reduced.

Usage

Create a file called INBUMP by following this annotated template:

variable	Fortran format	description
msfil	A80	surface file used as input to sphgen
boxfil	A80	box file used as input to chemgrid
prefix	A80	prefix for chemgrid files, used for output
resol	F	grid resolution - same as in chemgrid
pcon ccon	2F	contact distances for non-surface atoms
spcon sccon	2F	contact distances for surface atoms

Be sure to use the same grid resolution as used in the original chemgrid run. The second to last line contains the polar and non-polar contact distances to be applied to non-surface atoms. Generally these are values such as 2.3 and 2.8. The last line contains the polar and non-polar contact distances to be applied to active site surface atoms. The reduction in contact distances for surface atoms permits closer ligand contacts with the receptor and relies upon the minimizer to salvage the bad contacts. Often a reduction to 1.5 2.0 is sufficient (polar, non-polar, respectively). Further reduction to, say, 1.0 1.5 can provide even better results, but at the expense of CPU time. The best results are obtained when surface atoms are disappeared completely (i.e. 0.0 0.0), but here run-times can be prohibitive.

rebump will create a new bump map with the extension .bmp appended to the prefix specified on the third line of INBUMP. (To avoid overwriting an existing .bmp file, make sure to rename it before running rebump.) To utilize the newly created .bmp file with softer contacts when running DOCK, make sure it has the same prefix as the .vdw and .esp grid files created by chemgrid.

Curator: Daniel Gschwend, gschwend@cgl.ucsf.edu (rev. 1 September 1995)