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Darryl Reid, MSc., is a computational scientist and marketing representative for SimBioSys Inc. He obtained his bachelors of science in Chemistry from Memorial University of Newfoundland (Canada). Upon completion, he enrolled in the new Computational Science's Masters program at Memorial where his focus was on computational chemistry and its applications. From 2001 to 2004, Darryl was a key member of the Technical Analyst Support Program of C3.ca (Canada's leading High Performance Computing organization), at Memorial's Advanced Computation and Visualization Centre. In that role, he gained valuable experience in many areas of computational science in the academic world. Darryl joined the SimBioSys team in 2004.
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Virtual Ligand Screening with eHiTS
Darryl Reid, SimBioSys
Darryl Reid , Zsolt Zsoldos , Aniko Simon , Bashir S. Sadjad (1), and A Peter Johnson (2)
(1) SimBioSys Inc, 135 Queen's Plate Dr, Suite 520, Toronto, ON M9W 6V1, Canada
(2) School of Chemistry, University of Leeds, Leeds, LS2 9JT, United Kingdom
Virtual Ligand Screening (VLS) has become an integral part of the drug design process for many pharmaceutical companies. In protein structure based VLS the aim is to find a ligand that has a high binding affinity to the target receptor whose 3D structure is known. Ligand similarity searches also provide a very powerful method of quickly screening large databases of ligands to identify possible hits. This presentation will describe the docking tool eHiTS and its seamless integration with a new ligand-based pre-screening filter tool, eHiTS_Filter. eHiTS_Filter uses 23 surface point types (chemical property identifiers) to create a feature vector of active and presumed inactive ligands. The filter is then trained to recognize active ligands and can then be used to screen large databases of ligands extremely rapidly (5-7 ligands per second per cpu). eHiTS_Filter has been integrated into eHiTS to allow for docking poses to be generated for the top N% of the database as ranked by eHiTS_Filter. Enrichment results obtained over a wide range of receptor families consistently show that eHiTS_Filter is able to recover ~80% of the actives in the top 10% of a screened database.
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Docking and Screening
Darryl Reid, SimBioSys
In this workshop you will learn about the usage of eHiTS for accurate pose prediction as well as virtual screening. The computations will be performed on a Linux PC, using the eHiTS integrated Chemical Visualizer: CheVi. Some examples will be presented first that aim to illustrate the most common steps during the use of eHiTS flexible ligand docking tool: such as preparing the input files; setting up the run and analyzing / visualizing of the results. Subsequently you will investigate virtual screening using eHiTS docking alone and also combining it with eHiTS Filter. eHiTS Filter is a chemical feature descriptor method of the ligands. It works purely with ligand information and is looking for chemical features on the interaction surface of the ligands. Therefore eHiTS Filter can also work for virtual screening if there is no receptor structure available for the target.
Summary: You will learn about docking, accurate pose prediction, VHTS filtering and chemical features on the interaction surface of the ligands. Participants will also take home: A CD with a full suite of SimBioSys software and a license good for a period of 30 days from the end of the meeting.
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