Rational drug design in photopharmacology

Photopharmacology uses light to regulate the biological activity of drugs. This precise control is obtained through the incorporation of molecular photoswitches into bioactive molecules. A major challenge for photopharmacology is the rational design of photoswitchable drugs that show light-induced activation. Computer-aided drug design is an attractive approach toward more effective, targeted design.
This thesis describes the application and evaluation of rational drug design methods for predicting and interpreting the light-dependent activity of photopharmacogical agents. A wide range of informed, computer-aided design strategies was applied to the development of light-controlled tools, spanning from antibiotics to chemotherapeutics. The employed computational methods included docking and MD simulations for structure-based design, database searches to investigate molecular geometries, DFT calculations to study electronic properties. Future efforts in rational photopharmacology will need a combination of different methodologies and approaches to shed more light on the optical control of bioactive compounds.