rmoretti Staff Lv 1
There's a number of objectives. Most of them are there to keep the molecule going "too far" outside the range of acceptable parameters for drugs.
All objectives give +1000 points when fully satisfied, for a maximum of +12 000. Most objectives have a "Show" button which should highlight areas of concern in red. Even when fully satisfied, objectives may highlight groups which may eventually contribute, so it's not recommended to keep Show on at all times.
- Carboxylate Interaction - A bonus for keeping the hydrogen bonds the existing carboxylate is making. (Show highlights the protein atoms you need to make the hydrogen bonds to.)
- Ligand Hydrophobic Interaction - A bonus for keeping a hydrophobic interaction between the ligand and the protein. (Show highlights the protein residues the ligand should contact.)
- Peptide - Penalizes the formation of peptide-backbone-like groups. (Show highlights which parts of the ligand should be changed.)
- Torsion Quality - Keeps bond rotations in a good range. Using Wiggle or Tweak Ligand can fix bad torsions. (Show highlights torsions to be rotated.)
- Number of Rotatable Bonds - Intended to keep the ligand from getting too big and floppy. You can reduce rotatable bonds by deleting groups or forming rings. (Show highlights rotatable bonds.)
- Ligand TPSA - Topological Polar Surface Area - Keeps the polar surface area (including buried polar surface) low. To improve, try removing oxygens and nitrogens. (Show highlights atoms contributing to higher TPSA.)
- Ligand cLogP - A measure of polarity - Keeps the molecule from getting too hydrophobic. To improve, try adding polar oxygens and nitrogens. (Show highlights atoms contributing to higher cLogP.)
- Ligand Hydrogen Bond Donors - Keep the number of ligand hbond donors low. (Show highlights atoms contributing to higher cLogP.)
- Bad Groups - Gives a bonus for avoiding groups that aren't very drug-like, including enol, enamine, thiocarbonyl, hydroxylamines, geminal diols, alpha-beta unsaturated carbonyls, aliphatic alkanes, aliphatic alkenes, aliphatic ethers and others. (Show highlights groups at issue.)
- Element Counts - Limits certain element numbers: Desired P=0, S<=1, I<=1, Br<=1, Cl<=4, F<=4, N<=5 (Show highlights atoms of elements exceeding count.)
- Molecular Weight - Intended to keep the ligand small.
- Synthetic Accessibility - Identify molecules which are likely to be hard to make in the lab. (Show highlights regions of the molecule contributing to difficult synthesis.)