S Swagath, Nayak Prateek, Pal Kuntal
Department of Chemistry, School of Advanced Sciences, Vellore Institute of Technology, Vellore 632014, Tamil Nadu, India.
Department of Biosciences, School of Bioscience and Technology, Vellore Institute of Technology, Vellore 632014, Tamil Nadu, India.
ACS Omega. 2025 Jul 23;10(30):33270-33287. doi: 10.1021/acsomega.5c03268. eCollection 2025 Aug 5.
Class B G-protein coupled receptors (GPCRs) are significant therapeutic recipients in cardiovascular, neurological, and metabolic diseases. The human gut microbiome is a complex microbial ecology recently identified as a possible source of bioactive peptides that control host physiological functions. Candidate peptides were found using advanced bioinformatics tools including sequence homology analysis, structure modeling, and molecular docking. These peptides were then evaluated for their binding affinity and potential functional regulation of the GPCR activity. Molecular dynamics simulations offered additional insights regarding the stability and interaction diversity of peptide-receptor complexes, highlighting receptor conformational state of G-protein interaction. The findings identify unique microbial peptides capable of influencing class B GPCR function, providing important insights into microbiome-host interactions and therapeutic potential. This study emphasizes the gut microbiome's previously untapped potential as a source of GPCR modulators, opening up new avenues for microbiome-driven therapy approaches for metabolic and endocrine disorders.
B类G蛋白偶联受体（GPCRs）是心血管、神经和代谢疾病中重要的治疗靶点。人类肠道微生物群是一种复杂的微生物生态系统，最近被确定为控制宿主生理功能的生物活性肽的可能来源。使用包括序列同源性分析、结构建模和分子对接在内的先进生物信息学工具发现了候选肽。然后评估这些肽对GPCR活性的结合亲和力和潜在功能调节。分子动力学模拟提供了关于肽-受体复合物稳定性和相互作用多样性的更多见解，突出了G蛋白相互作用的受体构象状态。这些发现确定了能够影响B类GPCR功能的独特微生物肽，为微生物群-宿主相互作用和治疗潜力提供了重要见解。本研究强调了肠道微生物群作为GPCR调节剂来源此前未被开发的潜力，为代谢和内分泌疾病的微生物群驱动治疗方法开辟了新途径。
