eHiTS: electronic High
Throughput Screening
Zsolt Zsoldos1, Kenneth R.
Auerbach2
(1) SimBioSys
Inc., 135 Queen's Plate
Drive, Unit 355, Toronto, ON, M9W 6V1 Canada
(2) Center for
Neurologic Diseases -- Harvard Neurology Dept., Cambridge, MA
Abstract:
The flexible ligand docking problem is divided into two subproblems: pose/conformation search and scoring function. For successful virtual screening the search algorithm must be fast and able to find the optimal binding pose and conformation of the ligand, while the scoring function must be able to distinguish the binding pose of the active ligands from other poses and other ligands.
The presentation will give a brief overview of the fast, exhaustive docking algorithm of eHiTS. Special features of the software will be described, such as its ability to handle all possible protonations states of the receptor and the ligand in a single run saving hours of preparation and processing time compared to other docking protocols.
A new statistically derived empirical scoring function is employed by the latest version of the eHiTS software. The scoring function will be described in detail, including the use of temperature factors from the PDB files to consider the true statistical distribution of the interaction geometries that occur in binding sites.
The unique algorithms and data structures employed in eHiTS make it possible to achieve exhaustive, systematic coverage of the solution space in minutes. The ability of the eHiTS software to produce highly accurate docking results will be demonstrated on a very large and diverse validation set.
The ability of the scoring function to correctly separate active ligands from inactive ones will be demonstrated on a practical example. A series of compounds have been docked to the CDK5 receptor by eHiTS and the results are compared to experimental binding data showing good correlation with the eHiTS prediction.
For more information, see the company's web site: http://www.simbiosys.com/
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