A Structural Perspective on the Modulation of Protein-protein Interactions with Small Molecules

Demirel H. C., Dogan T., TUNÇBAĞ N.

CURRENT TOPICS IN MEDICINAL CHEMISTRY, vol.18, no.8, pp.700-713, 2018 (SCI-Expanded, Scopus) identifier identifier identifier

  • Publication Type: Article / Review
  • Volume: 18 Issue: 8
  • Publication Date: 2018
  • Doi Number: 10.2174/1568026618666180601080824
  • Journal Name: CURRENT TOPICS IN MEDICINAL CHEMISTRY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.700-713
  • Keywords: Protein-protein interactions, cellular processes, epigenetic regulation, pathways, structural information, molecules, CHRONIC MYELOID-LEUKEMIA, BINDING HOT-SPOTS, DRUG DISCOVERY, WEB SERVER, INTERACTION PREDICTION, MULTITARGET DRUGS, FREE-ENERGY, DATABASE, P53, DESIGN
  • Hacettepe University Affiliated: No

Abstract

Protein-Protein Interactions (PPIs) are the key components in many cellular processes including signaling pathways, enzymatic reactions and epigenetic regulation. Abnormal interactions of some proteins may be pathogenic and cause various disorders including cancer and neurodegenerative diseases. Although inhibiting PPIs with small molecules is a challenging task, it gained an increasing interest because of its strong potential for drug discovery and design. The knowledge of the interface as well as the structural and chemical characteristics of the PPIs and their roles in the cellular pathways is necessary for a rational design of small molecules to modulate PPIs. In this study, we review the recent progress in the field and detail the physicochemical properties of PPIs including binding hot spots with a focus on structural methods. Then, we review recent approaches for structural prediction of PPIs. Finally, we revisit the concept of targeting PPIs from a systems biology perspective and we refer to approaches that are usually employed when the structural information is not present.