10. Protein Structure
Modeling
Chia-Hsien Lee and Hsueh-Fen Juan∗
Graduate Institute of Biomedical Electronics and Bioinformatics
National Taiwan University, Taipei, Taiwan
∗[email protected]- Introduction
Protein structure plays important roles in various parts of biological research.
At first, researchers obtain protein structure experimentally with X-ray
diffraction to learn mechanism of action of their protein or biochemical
reaction steps of the enzyme, or the reason why some mutations bring
disaster on protein function. In summary, we learned a lot from those protein
structures, and thanks to them, our knowledge in biochemistry and certain
other biology disciplines have broadened.
Protein structure is now an important resource in computer-aided drug
discovery. For example, if one has a protein structure, he may use appropriate
algorithm to deduce how a compound (or ligand) binds to the protein and
evaluates the effectiveness of the ligand as a drug. Using this method we
developed a lot of drugs for many diseases. For example, in the work of
Harikishoreet al.,^1 crystal structure of hepatitis C virus NS5B is utilized to
find novel drugs targeting allosteric sites with docking and pharmacophore
techniques.
Despite the importance of protein structure information, obtaining them
experimentally is a tedious job. It may take many years to successfully obtain
crystallized pure protein which is suitable for X-Ray diffraction experiment.
Furthermore, for some proteins, it’s hard to obtain protein crystals of
acceptable quality. For example, membrane proteins are long considered
hard-to-form crystal; however, it may be far easier due to recent advance
113