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 the formed between the protein and a hydrophobic portion of paclitaxel. This is another example of the intermolecular forces that are at work.