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Contributors: David Mobley, Lee-Ping Wang, Hyesu Jang, Jeff Wagner, Chris Bayly, Josh Horton, Chaya Stern, Jessica Maat

Background:

  • The Open Force Field Initiative is working on developing optimization training data sets via a fingerprint and clustering method.

  • The aim of this project is to pull chemically diverse molecules from a range of data sets to survey a larger chemical space for our May release force field.

  • The Bayer set contains 5054 molecules that are large flexible pharmaceutically relevant molecules ranging from 12-30 heavy atoms.

Aim: The aim of this sub-experiment is to limit

  • Limit the number of conformers in a patented data set from Bayer for optimization data set.

    • Reduce data set to ~3 conformers/molecule.

Problem: The Bayer set contains large flexible drug molecules that range from 12-30 heavy atoms.

  • Current fingerprint & clustering methods result in 525 molecules & 16,242

...

  • conformers

...

  • .

  • Hypothesized contributors to large number of conformers:

    • Large molecule size

    • Excessive rotatable bonds

Approach:

  1. Try numerous size filtering strategies for molecule size that try to preserve chemical diversity and measure # of molecules and conformers.

  2. If #1 is not successful, move onto rotatable bond filtering.

  3. if #1 & #2 are not successful, move onto Fragmentation.

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