Article
Endocrinology & Metabolism
Mihaly Mezei, Rauf Latif, Terry F. Davies
Summary: Biophysical studies have shown that the TSH receptor undergoes posttranslational modifications, including dimerization. Molecular dynamics simulation of TSHR-TMD dimerization revealed that the dimeric subunits maintain the same relative orientation and distance. Differences in conformations were observed in small-molecule binding sites within the TMD.
Article
Chemistry, Medicinal
Sukanya Mozumder, Aritra Bej, Jayati Sengupta
Summary: This study used molecular dynamics simulations to reveal the functional regulation of 5-HT2AR with intact intracellular loops in ligand-free and different ligand-bound configurations. The results showed that the activation or inactivation of the receptor is primarily achieved through conformational transitions of its second and third intracellular loops, and ligand binding can control the receptor's conformation and thermodynamic properties, determining ligand-dependent functional selectivity.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Cell Biology
Veronica Murcia-Belmonte, Maria Tercero-Diaz, Diego Barrasa-Martin, Sandra Lopez de la Vieja, Marina Munoz-Lopez, Pedro F. Esteban
Summary: The X-linked form of Kallmann syndrome is caused by mutations in the ANOS1 gene, resulting in hypogonadotropic hypogonadism and anosmia. This study reveals that anosmin 1 can enhance the activation of the PK2/PKR2 pathway and modulate its biological effects. The N-terminal region of anosmin 1 interacts with PKR2, and the whey acidic protein domain is necessary for this modulatory activity, while the cysteine-rich and FnIII.1 domains may assist in binding to PKR2 and regulating receptor activation by PK2.
CELLULAR SIGNALLING
(2022)
Review
Cell Biology
Preeti Kumari Chaudhary, Soochong Kim
Summary: GPCRs play a crucial role in cancer progression, but the specific mechanisms of their involvement are still unclear. Studies have revealed the multifaceted impact of GPCRs on cancer development and the signaling pathways involved.
Article
Biochemistry & Molecular Biology
Sumin Lee, Seeun Kim, Gyu Rie Lee, Sohee Kwon, Hyeonuk Woo, Chaok Seok, Hahnbeom Park
Summary: This study explores the improvement in modeling and docking strategies for GPCR drug discovery through deep learning (DL) based protein structure predictions. It shows that substantial improvements have been achieved by correct functional-state modeling of receptors and receptor-flexible docking. The success rate of docking on DL-based model structures approaches that of cross-docking on experimental structures, showing over 30% improvement from previous pre-DL protocols. Best-practice modeling strategies and model confidence estimation metric proposed in this work can serve as a guideline for future computer-aided GPCR drug discovery scenarios.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Simona Daniele, Simona Saporiti, Stefano Capaldi, Deborah Pietrobono, Lara Russo, Uliano Guerrini, Tommaso Laurenzi, Elham Ataie Kachoie, Luca Palazzolo, Vincenzo Russo, Maria Pia Abbracchio, Ivano Eberini, Maria Letizia Trincavelli
Summary: GPR17, a key regulator of myelination, is activated by endogenous ligands and pro-inflammatory molecules. This study investigates the structural and functional interactions between GPR17 and chemokine receptors CXCR2 and CXCR4. The results show that these receptors can form heterodimers and modulate intracellular cAMP levels. This cross-talk between receptors could impact the neuroinflammatory environment associated with demyelinating events.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Mahmoud Elkazzaz, Amr Ahmed, Yousry Esam-Eldin Abo-Amer, Tamer Hydara, Abdullah Haikal, Dina N. Abd El Razek, Wafa Ali Eltayb, Xiling Wang, Tomasz M. Karpinski, Dalia Hamza, Basit Jabbar, Israa M. Shamkh
Summary: Despite ongoing research on the pathogenesis of COVID-19, much remains unknown. However, a recent study using molecular docking and molecular dynamics simulations found a high affinity between the SARS-CoV-2 spike protein and GnRHR and GPCRs. This discovery sheds light on the complex mechanisms involving neuroendocrine and peripheral organ involvement in COVID-19, and may lead to the identification of new drug targets.
Article
Biochemistry & Molecular Biology
Giacinto De Vivo, Fabio Crocetta, Miriam Ferretti, Roberto Feuda, Salvatore D'Aniello
Summary: By investigating 74 lophotrochozoan genomes, we discovered that the common ancestor of Lophotrochozoa possessed at least seven paralog groups of opsins, with divergent evolutionary histories in different phyla. Moreover, we identified opsin-related pseudopsins in Bilateria for the first time, potentially crucial in unraveling opsin evolution.
MOLECULAR BIOLOGY AND EVOLUTION
(2023)
Article
Multidisciplinary Sciences
N. Gao, Z. W. Yao, G. H. Lu, H. Q. Deng, F. Gao
Summary: The study found a new diffusion mechanism for <100> interstitial dislocation loops in BCC iron using self-adaptive accelerated molecular dynamics, which represents a significant step towards understanding the mechanical behavior and microstructure evolution of the material.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Tracy M. Josephs, Matthew J. Belousoff, Yi-Lynn Liang, Sarah J. Piper, Jianjun Cao, Daniel J. Garama, Katie Leach, Karen J. Gregory, Arthur Christopoulos, Debbie L. Hay, Radostin Danev, Denise Wootten, Patrick M. Sexton
Summary: This study provides insights into the mechanisms of class B1 GPCR activation by analyzing the structures and protein conformational dynamics of GPCRs.
Article
Biochemistry & Molecular Biology
Lorenzo Di Rienzo, Mattia Miotto, Edoardo Milanetti, Giancarlo Ruocco
Summary: Organisms have developed effective mechanisms to sense the external environment, and human-designed biosensors exploit this natural optimization. In the model organism Saccharomyces cerevisiae, the pheromone pathway can be engineered to recognize user-defined ligands. A computational procedure based on protein binding pocket optimization is proposed to select amino acid substitutions for the native yeast GPCR to recognize specific ligands.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Article
Multidisciplinary Sciences
Jingyi Zhao, Vincent DiGiacomo, Mariola Ferreras-Gutierrez, Shiva Dastjerdi, Alain Ibanez de Opakua, Jong-Chan Park, Alex Luebbers, Qingyan Chen, Aaron Beeler, Francisco J. Blanco, Mikel Garcia-Marcos
Summary: IGGi-11 selectively inhibits noncanonical activation of heterotrimeric G-protein signaling, blocking tumor cell signaling and inhibiting metastatic cancer cell invasion without interfering with canonical GPCR signaling mechanisms.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Pharmacology & Pharmacy
Sergi Ferre, Francisco Ciruela, Carmen W. Dessauer, Javier Gonzalez-Maeso, Terence E. Hebert, Ralf Jockers, Diomedes E. Logothetis, Leonardo Pardo
Summary: The study proposes the concept of GPCR-effect assemblies (GEMMAs), which are pre-assembled before receptor activation and allow more efficient interactions between specific signaling components. This offers an alternative model to the conventional collision coupling model and explains the differential properties of GPCRs in different cellular environments.
PHARMACOLOGY & THERAPEUTICS
(2022)
Review
Biochemistry & Molecular Biology
Ezgi Karaca, Chantal Prevost, Sophie Sacquin-Mora
Summary: Modeling protein-protein assemblies at the atomic level is challenging, but recent computational strategies using enhanced sampling, multi-scale modeling, and experimental data integration have provided insights into interface dynamics and their connection to the function of protein assemblies.
Article
Biochemistry & Molecular Biology
Beata Niklas, Bruno Lapied, Wieslaw Nowak
Summary: This study investigated compounds that target human and insect muscarinic acetylcholine receptors, which are novel targets for synergistic agents in pest control. The researchers used molecular docking and molecular dynamics simulation to study the conformational changes of these receptors in response to different ligands and proposed a potential strategy using bitopic ligands for better insect control.
Article
Infectious Diseases
Qi Wang, Bruce A. Rosa, Bakela Nare, Kerrie Powell, Sergio Valente, Dante Rotili, Antonello Mai, Garland R. Marshall, Makedonka Mitreva
PLOS NEGLECTED TROPICAL DISEASES
(2015)
Article
Chemistry, Medicinal
Flavio Ballante, Garland R. Marshall
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2016)
Article
Chemistry, Medicinal
Damodara N. Reddy, Flavio Ballante, Timothy Chuang, Adele Pirolli, Biagina Marrocco, Garland R. Marshall
JOURNAL OF MEDICINAL CHEMISTRY
(2016)
Article
Biochemistry & Molecular Biology
Scott A. Wildman, Xiange Zheng, David Sept, Jeffrey T. Auletta, Terrone L. Rosenberry, Garland R. Marshall
CHEMICAL BIOLOGY & DRUG DESIGN
(2011)
Letter
Biochemistry & Molecular Biology
Yat T. Tang, Rong Gao, James J. Havranek, Eduardo A. Groisman, Ann M. Stock, Garland R. Marshall
CHEMICAL BIOLOGY & DRUG DESIGN
(2012)
Article
Chemistry, Medicinal
Yat T. Tang, Garland R. Marshall
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2011)
Article
Chemistry, Medicinal
Laura Silvestri, Flavio Ballante, Antonello Mai, Garland R. Marshall, Rino Ragno
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2012)
Article
Biochemistry & Molecular Biology
Garland R. Marshall
JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN
(2012)
Article
Biochemistry & Molecular Biology
Flavio Ballante, Ira Musmuca, Garland R. Marshall, Rino Ragno
JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN
(2012)
Article
Biochemistry & Molecular Biology
Garland R. Marshall
JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN
(2013)
Article
Chemistry, Multidisciplinary
Xiange Zheng, Chuanjie Wu, Jay W. Ponder, Garland R. Marshall
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2012)
Article
Multidisciplinary Sciences
Daniel J. Kuster, Chengyu Liu, Zheng Fang, Jay W. Ponder, Garland R. Marshall
Letter
Multidisciplinary Sciences
Gregory V. Nikiforovich, Christina M. Taylor, Garland R. Marshall, Thomas J. Baranski
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2011)
Article
Biochemistry & Molecular Biology
Gregory V. Nikiforovich, Garland R. Marshall, Thomas J. Baranski
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2011)
Article
Biochemistry & Molecular Biology
Chengyu Liu, Jay W. Ponder, Garland R. Marshall
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2014)