REVIEW: Rational Design of Drugs Targeting G-Protein-Coupled Receptors: Ligand Search and Screening

---

Aleksandra P. Luginina¹, Andrey. N. Khnykin¹, Polina A. Khorn¹, Olga V. Moiseeva^1,2, Nadezhda A. Safronova¹, Vladimir A. Pospelov¹, Dmitrii E. Dashevskii¹, Anatolii S. Belousov¹, Valentin I. Borschevskiy^1,3,a*, and Alexey V. Mishin^1,b*

¹Research Center for Molecular Mechanisms of Aging and Age-Related Diseases, Moscow Institute of Physics and Technology, 141701 Dolgoprudny, Moscow Region, Russia

²Skryabin Institute of Biochemistry and Physiology of Microorganisms, Russian Academy of Sciences, 142290 Pushchino, Moscow Region, Russia

³Frank Laboratory of Neutron Physics, Joint Institute for Nuclear Research, 141980 Dubna, Moscow Region, Russia

Received January 10, 2024; Revised February 22, 2024; Accepted February 23, 2024

---

G protein-coupled receptors (GPCRs) are transmembrane proteins that participate in many physiological processes and represent major pharmacological targets. Recent advances in structural biology of GPCRs have enabled the development of drugs based on the receptor structure (structure-based drug design, SBDD). SBDD utilizes information about the receptor–ligand complex to search for suitable compounds, thus expanding the chemical space of possible receptor ligands without the need for experimental screening. The review describes the use of structure-based virtual screening (SBVS) for GPCR ligands and approaches for the functional testing of potential drug compounds, as well as discusses recent advances and successful examples in the application of SBDD for the identification of GPCR ligands.

---

KEY WORDS: drug development, GPCR, SBVS, functional tests

DOI: 10.1134/S0006297924050158

Publisher’s Note. Pleiades Publishing remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

---