Drugs are usually small molecules that must bind to protein molecules for therapeutic effect. Drug docking codes are used to determine how drugs will bind to these proteins, and how strongly. The problem with most docking codes currently is that while they model the motion of the drug, they do not take into account the motion of the protein, or do so only in a very limited fashion. This is because computing the motion of the entire protein, containing thousands of atoms, is computationally impractical, often impossible. The Conformation Explorer is a docking and motion prediction package currently being added to our molecular motions database (http://molmovdb.org, described at http://papers.gersteinlab.org/e-print/molmovdb-update-nar/preprint.pdf). It accelerates the large scale motions of the protein, allowing us to find drug-bound conformations significantly different from those observed experimentally. This movie shows glutamine binding protein binding a small glutamine molecule. The more compact, closed conformation coincides very closely with that known from experiment. The binding energy is within 0.8 kcal/mol (less than one hydrogen bond’s worth of energy) of an experimental estimate. [Movie]

Submitted by Samuel Flores, 6th Year Graduate Student