Design a Molecule – Hints and Tips: 1

Our current Design a Molecule competiton runs to 8th April. Here I will try to describe how I designed a new molecule using FieldAlign and any tips that I can think of to get you a headstart to the iPad2 that waits for the winner.

First you will need an evaulation or commercial license to FieldAlign and the files for the current competion. This competiton is to design a diverse molecule to mimic the 3-Phosphoinositide-Dependent Kinase-1 inhibitor recently described  by Medina et al. in J. Med. Chem. (DOI: 10.1021/jm101527u). The competition uses the alignment score from FieldAlign as the basis for judging entries so you will need to get as high a score as possible to be able to win. However, molecules with high 2D similarity to the starting point, or with high logP will receive a penalty to their score so that simply changing one atom in the starting point is unlikely to win. To help you we have aligned 200 randomly chosen fragments that you can use to grow or join together into a new molecule. Note that you don’t have to use the fragments to win.

Suggested workflow

  • Open the starting point “Cresset_March2011_starting_point” in FieldAlign
  • Look through the aligned fragments and mark any that you think that you can improve as “Favorites” by pressing the space bar
  • Delete the other fragments to give yourself a small project to work with:
    • Save the project file
    • Add a filter “Fav == false”
    • Highlight all the molecules by clicking on the top molecule, pressing shift and clicking on the bottom molecule
    • Press “Delete”
    • Remove the filter
  • Edit a copy of one (or more) of your favorite fragments, making the changes that you think will give you a better score the save it/them to the project
  • Run menu-> process, use the “Normal” settings
  • Repeat the design and alignment steps until you have the best molecule that you can get; be careful not to copy the reference molecule
  • Highlight you best scoring alignments and export them to an sdf file (File->Export->Selected alignments)
  • Submit your molecules. Note that the maximum file upload size is 70kb.

This is just my suggestion, there are many other ways to get a new molecule. The key thing is to output an aligned molecule in sdf format for uploading to the result page.  Whichever way you use, I wish you good luck.