Boston De Novo Design
Regine Bohacek, PhD
 
HOME
AlleGrow Modeling Software
How AlleGrow works
Growing using Monte Carlo
Growing heterocycles
Growing side chains
Optimization and ranking
FLO +
lzm graphical interface
Free Trial Version
Consulting and Modeling Services
Workshops
Publications
Background
Contact Us

 

 

Optimization by energy minimization

AlleGrow generates structures in low energy conformations. To further optimize the interactions between the newly generated AlleGrow structures and binding site atoms, each grown ligand is energy "minimized" in the presence of the binding site using the dockmin+ program from the FLO+ molecular modeling software. The procedure finds the nearest energy minimum of the AlleGrow structure and computes a predicted binding affinity.

Dockmin+

Dockmin+ is a energy minimization procedure developed by Colin McMartin for the FLO+ molecular modeling package.

Dockmin+ uses a molecular mechanics force field to find the nearest minimum to the original structure. Then dockmin+ uses a scoring function also developed by Colin McMartin to evaluate the ligand/binding site interactions.

Scoring Function

The scoring function used by the FLO+ suite of programs uses a potential function containing the following terms:

  • Contact Energy
  • Hydrogen Bond energy
  • Entropy
  • Polar Desolvation
  • Internal Free Energy
  • Repulsion

Ranking AlleGrow output with post-grow+

The single command: post-grow+ will

  • energy minimize each AlleGrow generated structure in the binding site
  • compute a predicted binding energy
  • retain only the top scoring conformation of each molecule
  • rank all the structures by score and cluster them into multi structure files with each file containing molecules with similar scores

Now the user can easily inspect the ranked structures with lzm.