Promiscuity in drug discovery on the verge of the structural revolution: recent advances and future chances

Research output: Contribution to journalReview articleContributedpeer-review

Contributors

Abstract

INTRODUCTION: Promiscuity denotes the ability of ligands and targets to specifically interact with multiple binding partners. Despite negative aspects like side effects, promiscuity is receiving increasing attention in drug discovery as it can enhance drug efficacy and provides a molecular basis for drug repositioning. The three-dimensional structure of ligand-target complexes delivers exclusive insights into the molecular mechanisms of promiscuity and structure-based methods enable the identification of promiscuous interactions. With the recent breakthrough in protein structure prediction, novel possibilities open up to reveal unknown connections in ligand-target interaction networks.

AREAS COVERED: This review highlights the significance of structure in the identification and characterization of promiscuity and evaluates the potential of protein structure prediction to advance our knowledge of drug-target interaction networks. It discusses the definition and relevance of promiscuity in drug discovery and explores different approaches to detecting promiscuous ligands and targets.

EXPERT OPINION: Examination of structural data is essential for understanding and quantifying promiscuity. The recent advancements in structure prediction have resulted in an abundance of targets that are well-suited for structure-based methods like docking. In silico approaches may eventually completely transform our understanding of drug-target networks by complementing the millions of predicted protein structures with billions of predicted drug-target interactions.

Details

Original languageEnglish
Pages (from-to)973-985
Number of pages13
JournalExpert opinion on drug discovery
Volume18
Issue number9
Publication statusPublished - 2023
Peer-reviewedYes

External IDs

Scopus 85165679126

Keywords

Keywords

  • Humans, Ligands, Drug Discovery/methods, Proteins/metabolism, Drug-Related Side Effects and Adverse Reactions

Library keywords