Fragment-Based Drug Discovery

This represents the binding of the anti-cancer drug, paclitaxel, to the anti-apoptotic protein, Bcl-xl. The protein includes six alpha helices and no beta sheets.

Bcl-xl is a protein that is over-expressed in many forms of cancers and is an initiator of tumor formation. There is also evidence that Bcl-xl expression may also contribute to chemo-resistance. Paclitaxel has been show to effectively inhibit the over-expression of this protein thereby inducing tumor regression and increasing chemo-sensitivity.

Shown here is the interaction between paclitaxel and the protein via . The hydrogen bond is formed between an oxygen from the sulfoxone portion of the drug to an "N-H" group of a glycine amino acid. This forms one of the intermolecular or "weak" bonds between the drug and protein.

Shown here is a sort of formed between the protein (red) and hydrophobic, or "water hating", portions of paclitaxel. This is an example of hydrophobic bonding formed by intermolecular forces between some hydrophobic sections of the protein with hydrophobic portions of the ligand.

Click on each amino acid to view the hydrophobic interactions with the ligand: