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Interrogating HIV integrase for compounds that bind- a SAMPL challenge

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Abstract

Tremendous gains and novel methods are often developed when people are challenged to do something new or difficult. This process is enhanced when people compete against each other-this can be seen in sport as well as in science and technology (e.g. the space race). The SAMPL challenges, like the CASP challenges, aim to challenge modellers and software developers to develop new ways of looking at molecular interactions so the community as a whole can progress in the accurate prediction of these interactions. In order for this challenge to occur, data must be supplied so the prospective test can be done. We have supplied unpublished data related to a drug discovery program run several years ago on HIV integrase for the SAMPL4 challenge. This paper describes the methods used to obtain these data and the chemistry involved.

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Acknowledgments

DLM acknowledges the financial support of the National Institutes of Health (1R15GM096257-01A1), and computing support from the UCI GreenPlanet cluster, supported in part by NSF Grant CHE-0840513. The work was supported by a commercial ready grant COMO4229 from the Commonwealth of Australia, Department of Innovation, Industry, Science and Research to Avexa Pty Ltd. We thank the Australian Synchrotron and the beamline scientists at MX1 and MX2 for their help in data collection; and the Collaborative Crystallisation Centre for producing the protein crystals used in this study. Compounds in this study were prepared for Avexa Pty Ltd by Dr G. Le (now at Alchemia Pty Ltd), Dr J.A. Smith (now at F.B. Rice Pty Ltd), SYNthesis med chem Pty Ltd, Dr J. Spencer (now at the University of Sussex, UK) and Dr H. Patel at the time at the University of Greenwich, UK. We thank OpenEye Scientific Software for a license to their software.

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Authors and Affiliations

  1. CSIRO, Parkville, VIC, Australia

    Thomas S. Peat, Olan Dolezal & Janet Newman

  2. UC Irvine, Irvine, CA, USA

    David Mobley

  3. Chemocopeia Pty Ltd, Melbourne, VIC, Australia

    John J. Deadman

Authors
  1. Thomas S. Peat
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  2. Olan Dolezal
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  3. Janet Newman
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  4. David Mobley
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  5. John J. Deadman
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Corresponding author

Correspondence to Thomas S. Peat.

Electronic supplementary material

Below is the link to the electronic supplementary material.

10822_2014_9721_MOESM1_ESM.xlsx

Supporting Information: In the Supporting Information, we provide tables with compound IDs and isomeric SMILES strings for all of the compounds examined here, as well as for a more extensive set of nonbinders which were tested. The PDB codes for the 55 new structures used in the challenge are also provided in a table. (XLSX 12 kb)

Supplementary Material 2 (XLSX 141 kb)

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Peat, T.S., Dolezal, O., Newman, J. et al. Interrogating HIV integrase for compounds that bind- a SAMPL challenge. J Comput Aided Mol Des 28, 347–362 (2014). https://doi.org/10.1007/s10822-014-9721-7

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  • DOI: https://doi.org/10.1007/s10822-014-9721-7

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