Molecular modeling is a computer aided technique used to study and visualize the atomic structure of a protein target and the interaction with its natural ligand or the innovative compounds produced by Actelion’s medicinal chemists. Structural knowledge of protein-small-molecule complexes, and the possibility of visualizing them, allows experts with different scientific backgrounds to communicate on the basis of a common understanding.

Protein crystallographers solve (determine) the three-dimensional structures of drug target proteins and complexes of some drug targets with Actelion’s compounds. The proteins of interest are provided by specialists in ‘large’ amounts (milligrams), and at very high purity. Suitable crystals are then X-rayed, and the diffraction intensities (the way in which the crystal deflects the X-ray beam) are measured. The pattern produced by the diffraction is subsequently ‘translated’ using powerful computers and cutting edge software into a three-dimensional protein structure.

Modeling experts then analyze the new protein structure, and possibly compare multiple structures. in order to deduce enzyme/receptor mechanisms and suggest ligands that can modulate protein function.

Together, these experts provide structural information and interpretation which can be used to guide chemists in designing new compounds. It is important to note that even the most sophisticated tools providing the highest quality data cannot yet replace human expertise and the correct interpretation of the data generated.

Three-dimensional projection of highly complex protein structures with thousands of atoms offers insight to experts of different scientific disciplines. The visualization helps with understanding, and boosts the creativity of the project groups, and ultimately of the whole drug discovery unit.