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[Blog]
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[News]
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Can we trust docking results?
Sept 2010 IBM Systems and Technology Group releases a white paper with eHiTS and Cell
Oct 2008
EPA's ToxCastTM project will use SimBioSys' eHiTS as docking engine
Nov, 2007
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[Events]
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| 243rd ACS
Mar 25-29, 2012
San Diego, CA
see >> more
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eHiTS: a fast, exhaustive
flexible ligand docking engine
Zsolt Zsoldos1, Aniko Simon1,
Darryl Reid1, Bashir Sadjad1, A. Peter Johnson2
(1) SimBioSys Inc., 135 Queen's Plate
Drive, Unit 355, Toronto, ON, M9W 6V1 Canada
(2) Institute for Computer
Applications in Molecular Sciences (ICAMS),
School of Chemistry,
University of
Leeds, Leeds, UK LS2 9JT
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 describe, analyze and validate the search engine
of the eHiTS flexible ligand docking software. An innovative geometric
shape and chemical feature graph representation is used for both the
ligand and the receptor cavity. This representation enables eHiTS
to rapidly flood-dock all rigid fragments into the receptor cavity
systematically mapping out all sterically feasible poses in a matter of
seconds. The number of rigid fragment
poses generated typically ranges from tens to hundreds of
thousands and these cover the entire binding site with fine
resolution (~0.3 Angstrom RMSD from each other). The use of any
exponential graph matching algorithm (e.g. clique detection) on these
large sets of poses would be prohibitive in terms of CPU complexity due
to the combinatorial explosion. Therefore, a new algorithm was invented
that can process the poses with linear time complexity and is
guaranteed to find the solution with the optimal global score. The
flexible chains are fitted back to the selected rigid fragment poses
followed by a quadratic-convergence local energy minimization on the
reconstructed ligand.
The unique algorithms and data structures employed in eHiTS make it
possible to achieve exhaustive, systematic coverage of the
solution space in minutes at an accuracy level that would require
millions of CPU years with brute force exhaustive evaluation of the
entire search space using the same resolution. Thus, the eHiTS search
engine produces highly accurate docking poses at a speed making it
practical for virtual high throughput screening.
Validation results of the eHiTS search engine will be presented to
demonstrate the ability of the program to accurately reproduce known
binding poses on a large set of PDB complexes.
For
more information, see the company's web site: http://www.simbiosys.com/
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Full Presentation
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