[Product Releases]

• eHiTS v9.1
• Score v9.1
• LASSO v9.1
• CheVi
• SPROUT
• ARChem
• CAESA
• CLiDE v5

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[News]

Can we trust docking results?
Sept 2010

IBM Systems and Technology Group releases a white paper with eHiTS and Cell
Oct 2008

EPA's ToxCast^TM project will use SimBioSys' eHiTS as docking engine
Nov, 2007

[Events]

243rd ACS
Mar 25-29, 2012
San Diego, CA
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Presentation:

VHTS with eHiTS and de-novo Design with SPROUT: A Powerful Strategy for Drug Discovery

Dr. Katie Simmons (1), Prof. A. Peter Johnson (2), Dr. Aniko Simon (3) ,  
(1) University of Leeds, School of Chemistry, Leeds, LS2 9JT, UK
(2) KeyModule Ltd., Leeds, UK http://www.keymodule.co.uk
(3) SimBioSys Inc., Toronto, Canada http://www.simbiosys.com/

In silico molecular docking techniques, such as virtual high-throughput screening (VHTS), are powerful approaches to the discovery of new enzyme inhibitors. Additionally, de-novo design is a complementary strategy for inhibitor discovery. Here, by using the structural features present within the enzyme only, new inhibitor designs are built-up sequentially according to the requirements of the targeted binding site. Therefore, de-novo design is an important technique to use in parallel with VHTS in a particular hit identification campaign, as a good de-novo design program will examine structural space larger by many orders of magnitude than that of most virtual libraries currently used for this purpose.

We have recently applied both the de-novo molecular design computer program SPROUT, and the VHTS program eHiTS to a number of therapeutically attractive enzyme targets and have, in the majority of cases under study, rapidly identified inhibitors in the micromolar range or better.

References:

1. Bioorganic & Medicinal Chemistry Letters, Volume 19, Issue 23, 1 December 2009, Pages 6770-6774
2. Discovery of novel non-peptide inhibitors of BACE-1 using virtual high-throughput screening, N. Yi Mok, James Chadwick, Katherine A.B. Kellett, Nigel M. Hooper, A. Peter Johnson, Colin W.G. Fishwick; doi:10.1016/j.bmcl.2009.09.103, J. Med. Chem. 2009, 52, 2683 - 2693
3. Structure-Based Design, Synthesis, and Characterization of Inhibitors of Human and Plasmodium falciparum Dihydroorotate Dehydrogenases, Matthew Davies,Timo Heikkila, Glenn A. McConkey, Colin W. G. Fishwick, Mark R. Parsons, and A. Peter Johnson; Mol Microbiol. 2009 Apr;72(2):335-43. Epub 2009 Mar 3.
4. The nature of Staphylococcus aureus MurA and MurZ and approaches for detection of peptidoglycan biosynthesis inhibitors; Blake KL, O'Neill AJ, Mengin-Lecreulx D, Henderson PJ, Bostock JM, Dunsmore CJ, Simmons KJ, Fishwick CW, Leeds JA, and Chopra I.;

Workshop

User-friendly Ligand LASSOing and Docking, Results Analysis and Visualization

Dr. Katie Simmons (University of Leeds, UK)

Participants in this workshop will experience applying different methods and tools that can make virtual screening more productive. eHiTS LASSO is a ligand-based filter that uses the chemical features of a ligand surface to create a pseudo-pharmacophore for rapid screening of large databases. eHiTS is an accurate fragment-based docking program for both virtual screening and binding pose prediction of ligands. CheVi is an advanced visualization package specifically designed to help users analyze how ligands interact with receptors. In addition, CheVi acts as a front-end graphical user interface to run eHiTS LASSO and eHiTS screening and docking jobs.

The workshop will describe a typical work-flow from database to lead and show how tools from SimBioSys can make the process more effective using the plasmodium falciparum dihydroorotate dehydrogenase inhibitor, A77-1726 as an example. Users will get a hands-on lesson on how to use all the tools described above, with specific attention to analysis of interaction results.

Class members working in small groups will be able to apply the virtual screening methods during the week to their case studies.

Participants will also take home: A FREE unlimited version of the CheVi visualization tool and a two (2) month evaluation version of eHiTS and the eHiTS LASSO.

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