Computational Molecular Design
Dr. Marcus Weber
Erlinda C. Körnig
Staff | Projects | Publications
Computational Molecular Design is dealing with the mathematical modelling of flexibility of biomolecules and its application in the field of Virtual Screening. The central topics are "metastability" and "conformational ensembles".
Fast sampling methods have been developed for complete decomposition of the conformational space of drug-like molecules into metastable subregions. The decomposed "eigenconformations" of the molecules are used as input for subsequent methods in the screening pipeline.
The alignment and docking procedures generate flexibilty via a linear combination of "eigenconformations". A lead structure of the drug development process or the active site of a target protein serve as the objective function in a point matching problem.
The scoring approach extends conventional scoring functions with an additional term of conformational entropy, which is derived from thermodynamically calculated conformational ensembles.
New rigorous thermodynamical sampling and integration methods have been developed. Fast mixing of Markov chains and exact thermodynamical weights for "inexact" distributions can be calculated using information derived from a complete decomposition of conformational space.