Biophysical and computational techniques are part of nearly every inhibitor design project in the Schirmeister Lab. However, understanding the underlying molecular mechanisms is the key to succes. In a longstanding collaboration with the Engels' Lab of theoretical chemistry at the JMU Würzburg, a protocol for the design of customized covalent (reversible) inhibitors was established using rhodesain as a model cystein protease.
Schirmeister, T., Kesselring, J., Jung, S., et al. Quantum Chemical-Based Protocol for the Rational Design of Covalent Inhibitors. J. Am. Chem. Soc. 2016, 138, 27, 8332–8335.
With access to state of the art instruments, the underlying thermodynamic and kinetic parameters of (covalent) binding are further elucidated for several model systems.