Chemical-feature based pharmacophore models have been established as state-of-the-art technique for bioactivity prediction. While in ligand-based drug design, chemical feature-based pharmacophore creation from a set of bio-active molecules is a frequently chosen approach, structure-based pharmacophores are still lacking the reputation to be an alternative or at least a supplement to docking tec...

A new pharmacophore-based modeling procedure, including homology modeling, pharmacophore study, flexible molecular docking, and long-time molecular dynamics (MD) simulations, was employed to construct the structure of the human 5-HT(2C) receptor and determine the characteristics of binding modes of 5-HT(2C) receptor agonists. An agonist-receptor complex has been constructed based on homology mo...

The importance of the consideration of water molecules in the structural interpretation of ligand-derived pharmacophore models is explored. We compare and combine results from recently introduced methods for bound-water molecule identification in protein binding sites and ligand-superposition-based pharmacophore derivation, for the interpretation of ligand-derived pharmacophore models. In the a...

Tautomeric rearrangements of a molecule lead to distinct equilibrated structural states of the same chemical compound that may differ significantly in molecular shape, surface, nature of functional groups, hydrogenbonding pattern and other derived molecular properties [1]. Especially for the structure-based pharmacophore modeling of ligand-protein complexes [2], knowledge of the most favorable ...

We describe a novel method to develop energetically optimized, structure-based pharmacophores for use in rapid in silico screening. The method combines pharmacophore perception and database screening with protein ligand energetic terms computed by the Glide XP scoring function to rank the importance of pharmacophore features. We derive energy-optimized pharmacophore hypotheses for 30 pharmaceut...