title: Virtual screening for compounds that mimic protein-protein interface epitopes.
abstract: Modulation of protein-protein interactions (PPI) has emerged as a new concept in rational drug design. Here, we present a computational protocol for identifying potential PPI inhibitors. Relevant regions of interfaces (epitopes) are predicted for three-dimensional protein models and serve as queries for virtual compound screening. We present a computational screening protocol that incorporates two different pharmacophore models. One model is based on the mathematical concept of autocorrelation vectors and the other utilizes fuzzy labeled graphs. In a proof-of-concept study, we were able to identify serine protease inhibitors using a predicted trypsin epitope as query. Our virtual screening framework may be suited for rapid identification of PPI inhibitors and suggesting bioactive tool compounds.
authors.affiliation: Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH), Institute of Pharmaceutical Sciences, Wolfgang-Pauli-Str. 10, CH-8093 Zurich, Switzerland.
authors.forename: Tim
authors.initials: T
authors.lastname: Geppert
authors.forename: Felix
authors.initials: F
authors.lastname: Reisen
authors.forename: Max
authors.initials: M
authors.lastname: Pillong
authors.forename: Volker
authors.initials: V
authors.lastname: Hähnke
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Tanrikulu
authors.forename: Christian P
authors.initials: CP
authors.lastname: Koch
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Perna
authors.forename: Tatiana Batista
authors.initials: TB
authors.lastname: Perez
authors.forename: Petra
authors.initials: P
authors.lastname: Schneider
authors.forename: Gisbert
authors.initials: G
authors.lastname: Schneider
mesh_terms: D000939:Epitopes / Q000737:chemistry*; D008958:Models, Molecular; D018716:Molecular Mimicry; D011506:Proteins / Q000737:chemistry*; D012984:Software
chemical_list: D000939:Epitopes; D011506:Proteins