Monday, May 26, 2008

Protein Flexibility and False Positives detection.

Standard hit identification procedure with QUANTUM software implies screening of a large compound library against a given protein target. An example of such procedure for a small set of compounds with known activities is discussed in another blog entry.

Let us show first that a calculation with flexible protein gives a reasonable prediction of the binding free energy. To do that we selected a set of ~200 protein - ligand complexes from the BindingDB database. The protein-ligand pairs were selected mainly so that the complex is small and therefore the whole calculation is fast. The results are represented on the Figure. The horizontal and the vertical axis represent the calculated and the experimental value of the binding free energy calculated from the complexed positions of the ligand within the protein.

The correlation is clearly there and in a few days I will show that the calculated values demonstrate not only the accuracy, but also a good selectivity.

The other Figure represents the correlation between the results of rigid receptor fast docking procedure (horizontal axis) and the fully flexible binding free energies (vertical axis). Although the rigid protein force field has a decent correlation, it fails to recognize electrostatic clashes and thus leads to a fairly large amount of false positives among the predicted ligands. Only about 10% of all the ligands, all originally predicted in the muM range survives as binders. The trend is also clear: all the binding energy values increase (fully flexible force field gives less binders than the rigid calculation would suggest).

Saturday, May 24, 2008

Quantum Pharmaceuticals and Tibotec Pharmaceuticals enter antiviral drug discovery collabortaion.

Quantum Pharmaceuticals announces a drug discovery collaboration with Tibotec Pharmaceuticals (subsidiary of Johnson & Johnson).

Under the terms of the agreement Quantum Pharmaceuticals will provide Tibotec Pharmaceuticals with the family of anti-viral drug hits. The drug hits were discovered by Quantum Pharmaceuticals using its proprietary discovery technology. Tibotec Pharmaceuticals is to further evaluate and develop transferred molecules. Financial terms of the collaboration were not disclosed.

About Tibotec Pharmaceuticals BVBA
Tibotec BVBA is a global pharmaceutical and research development company. The Company's main research and development facilities are in Mechelen, Belgium with offices in Yardley, Pa. and Cork, Ireland. Tibotec is dedicated to the discovery and development of innovative HIV/AIDS and hepatitis C drugs, and anti-infectives for diseases of high unmet medical need.

About Quantum Pharmaceuticals
Quantum Pharmaceuticals is a drug discovery company based in Moscow, Russia specializing in small molecule screening and design through the use of its proprietary technology platform.

Wednesday, May 21, 2008

Computer aided drug design video from Quantum Pharma


Molecular modelling software of Quantum Pharmaceuticals is used to dock small molecule to active site of target protein. The molecular docking on flexible protein is explored. The Quantum docking software is available for free use at LeadFinding.com, the online hit-to-lead optimization service to filter and profile chemical compounds in chemical database of ChemDiv - organic chemistry supplier.