Skip to main content
U.S. Department of Energy
Office of Scientific and Technical Information

A genetic algorithm based method for docking flexible molecules

Technical Report ·
DOI:https://doi.org/10.2172/10132318· OSTI ID:10132318
 [1]; ;  [2]
  1. Sandia National Labs., Livermore, CA (United States)
  2. Sterling-Winthrop Inc., Collegeville, PA (United States)

The authors describe a computational method for docking flexible molecules into protein binding sites. The method uses a genetic algorithm (GA) to search the combined conformation/orientation space of the molecule to find low energy conformation. Several techniques are described that increase the efficiency of the basic search method. These include the use of several interacting GA subpopulations or niches; the use of a growing algorithm that initially docks only a small part of the molecule; and the use of gradient minimization during the search. To illustrate the method, they dock Cbz-GlyP-Leu-Leu (ZGLL) into thermolysin. This system was chosen because a well refined crystal structure is available and because another docking method had previously been tested on this system. Their method is able to find conformations that lie physically close to and in some cases lower in energy than the crystal conformation in reasonable periods of time on readily available hardware.

Research Organization:
Sandia National Labs., Livermore, CA (United States)
Sponsoring Organization:
USDOE, Washington, DC (United States)
DOE Contract Number:
AC04-76DR00789
OSTI ID:
10132318
Report Number(s):
SAND--93-8688; ON: DE94007525
Country of Publication:
United States
Language:
English