The ligand chosen for this tutorial, tazobactam, is an inhibitor of the betalactamases, enzymes which destroy penicillin and its relatives. There are infectious bacterial strains which have developed betalactamases so that they are resistant to penicillin-like antiobiotics. There is a significant effort among pharmaceutical companies to find a solution to the disarming by infectious bacteria of one of the most common antibiotic families.

Penicillin core Amoxicillin Methicillin

piperacillin tazobactam

One solution is tazobactam, which is marketed in combination with piperacillin, binds in the active site of beta-lactamase preventing the beta-lactamase from destroying the pipericillin. From the chemical structure it is clear that the molecule resembles closely the penicillin type antibiotics and has a good chance at binding int the active site of the betalactmases. It appears that the mechanism of inhibition is the chemical bonding of a fragment to an active site serine, leaving the active site permanently disabled. The chemical binding of the fragment occurs as part of the degrading of the tazobactam molecule.

This tutorial is an introduction to setting up and starting simulations of protein-ligand systems with a nonstandard ligand. The aim of the project is to model the docked ligand to get structural and thermodynamic data about the bound ligand.

The practical skills demonstrated are: