VAMMPIRE: A Matched Molecular Pairs Database for Structure-Based Drug Design and Optimization

Structure-based optimization to improve the affinity of a lead compound is an established approach in drug discovery. Knowledge-based databases holding molecular replacements can be supportive in the optimization process. We introduce a strategy to relate the substitution effect within matched molecular pairs (MMPs) to the atom environment within the cocrystallized protein–ligand complex. Virtually Aligned Matched Molecular Pairs Including Receptor Environment (VAMMPIRE) database and the supplementary web interface (http://vammpire.pharmchem.uni-frankfurt.de) provide valuable information for structure-based lead optimization.