Design a Molecule - May 2011

Our previous Design a Molecule Competition proved so popular that we are running another one! The competition opens today, May 16 and runs until June 20 and once again we will be giving a new iPad2 to the designer of the best molecule. Following a suggestion from Chris Swain at Macs in Chemistry we have chosen a target from the fight against malaria. We would like you to design the highest scoring molecule (in FieldAlign) that mimics a known ligand for Plasmodium falciparum dihydroorotate dehydrogenase as seen in the protein ligand crystal structure 3O8A.

To enter the competition, register here and we will send you an download link and license file for FieldAlign and FieldView together with the ligand and protein from 3O8A. 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 25 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.

Here is my suggested workflow (it is the same as last month):

• Open the starting point “Starting_project_May11” 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 your 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 which should be enough for 5-10 entries.

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.