Molecular interaction fingerprint approaches for GPCR drug discovery

Research output: Contribution to journalReviewResearchpeer-review

Márton Vass, Albert J. Kooistra, Tina Ritschel, Rob Leurs, Iwan JP de Esch, Chris de Graaf

Protein–ligand interaction fingerprints (IFPs) are binary 1D representations of the 3D structure of protein–ligand complexes encoding the presence or absence of specific interactions between the binding pocket amino acids and the ligand. Various implementations of IFPs have been developed and successfully applied for post-processing molecular docking results for G Protein-Coupled Receptor (GPCR) ligand binding mode prediction and virtual ligand screening. Novel interaction fingerprint methods enable structural chemogenomics and polypharmacology predictions by complementing the increasing amount of GPCR structural data. Machine learning methods are increasingly used to derive relationships between bioactivity data and fingerprint descriptors of chemical and structural information of binding sites, ligands, and protein–ligand interactions. Factors that influence the application of IFPs include structure preparation, binding site definition, fingerprint similarity assessment, and data processing and these factors pose challenges as well possibilities to optimize interaction fingerprint methods for GPCR drug discovery.

Original languageEnglish
JournalCurrent Opinion in Pharmacology
Volume30
Pages (from-to)59-68
Number of pages10
ISSN1471-4892
DOIs
Publication statusPublished - 1 Oct 2016
Externally publishedYes

ID: 199352356