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Mechanistic Insights into Specific G Protein Interactions with Adenosine Receptors

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Download Hi-Res ImageDownload to MS-PowerPointCite This:J. Phys. Chem. B 2019, 123, 30, 6462-6473
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    Mechanistic Insights into Specific G Protein Interactions with Adenosine Receptors
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    The Journal of Physical Chemistry B

    Cite this: J. Phys. Chem. B 2019, 123, 30, 6462–6473
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    https://doi.org/10.1021/acs.jpcb.9b04867
    Published July 8, 2019
    Copyright © 2019 American Chemical Society
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    Abstract

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    Coupling between G-protein-coupled receptors (GPCRs) and the G proteins is a key step in cellular signaling. Despite extensive experimental and computational studies, the mechanism of specific GPCR–G protein coupling remains poorly understood. This has greatly hindered effective drug design of GPCRs that are primary targets of ∼1/3 of currently marketed drugs. Here, we have employed all-atom simulations using a robust Gaussian accelerated molecular dynamics (GaMD) method to decipher the mechanism of the GPCR–G protein interactions. Adenosine receptors (ARs) were used as model systems based on very recently determined cryo-EM structures of the A1AR and A2AAR coupled with the Gi and Gs proteins, respectively. Changing the Gi protein to the Gs led to increased fluctuations in the A1AR and agonist adenosine (ADO), while agonist 5′-N-ethylcarboxamidoadenosine (NECA) binding in the A2AAR could be still stabilized upon changing the Gs protein to the Gi. Free energy calculations identified one stable low-energy conformation for each of the A1AR-Gi and A2AAR-Gs complexes as in the cryo-EM structures, similarly for the A2AAR-Gi complex. In contrast, the ADO agonist and Gs protein sampled multiple conformations in the A1AR-Gs system. GaMD simulations thus indicated that the A1AR preferred to couple with the Gi protein to the Gs, while the A2AAR could couple with both the Gs and Gi proteins, being highly consistent with experimental findings of the ARs. More importantly, detailed analysis of the atomic simulations showed that the specific AR-G protein coupling resulted from remarkably complementary residue interactions at the protein interface, involving mainly the receptor transmembrane 6 helix and the Gα α5 helix and α4-β6 loop. In summary, the GaMD simulations have provided unprecedented insights into the dynamic mechanism of specific GPCR–G protein interactions at an atomistic level.

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    • Table S1 and Figures S1–S14 showing representation of the computational model of AR-G protein system, time courses of reaction coordinates and 2D-PMF, RMSF of AR-G protein, sequence conservation across ARs, and residue interactions between the Gα and receptor in the “overactive” state of the A1AR-Gs (PDF)

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    23. Hung N. Do, Jinan Wang, Keya Joshi, Kushal Koirala, Yinglong Miao. Gaussian Accelerated Molecular Dynamics in Drug Discovery. 2024, 21-43. https://doi.org/10.1002/9783527840748.ch2
    24. Jian Wang, Wanchun Yang, Lu Zhao, Benzheng Wei, Jianzhong Chen. Binding Mechanism of Inhibitors to BRD4 and BRD9 Decoded by Multiple Independent Molecular Dynamics Simulations and Deep Learning. Molecules 2024, 29 (8) , 1857. https://doi.org/10.3390/molecules29081857
    25. Congcong Shen, Jie Yin, Min Wang, Zhiping Yu, Xin Xu, Zhongshun Zhou, Yingshi Hu, Caijuan Xia, Guodong Hu. Mutations influence the conformational dynamics of the GDP/KRAS complex. Journal of Biomolecular Structure and Dynamics 2024, , 1-14. https://doi.org/10.1080/07391102.2024.2331627
    26. Zhiping Yu, Zhen Wang, Xiuzhen Cui, Zanxia Cao, Wanyunfei Zhang, Kunxiao Sun, Guodong Hu. Conformational States of the GDP- and GTP-Bound HRAS Affected by A59E and K117R: An Exploration from Gaussian Accelerated Molecular Dynamics. Molecules 2024, 29 (3) , 645. https://doi.org/10.3390/molecules29030645
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    38. Lifei Wang, Yan Wang, Yingxia Yu, Dong Liu, Juan Zhao, Lulu Zhang. Deciphering Selectivity Mechanism of BRD9 and TAF1(2) toward Inhibitors Based on Multiple Short Molecular Dynamics Simulations and MM-GBSA Calculations. Molecules 2023, 28 (6) , 2583. https://doi.org/10.3390/molecules28062583
    39. H.Y. Bao, W. Wang, H.B. Sun, J.Z. Chen. Binding modes of GDP, GTP and GNP to NRAS deciphered by using Gaussian accelerated molecular dynamics simulations. SAR and QSAR in Environmental Research 2023, 34 (1) , 65-89. https://doi.org/10.1080/1062936X.2023.2165542
    40. Baylee J. O'Brien, Erika Y. Faraoni, Lincoln N. Strickland, Zhibo Ma, Victoria Mota, Samantha Mota, Xuebo Chen, Tingting Mills, Holger K. Eltzschig, Kathleen E. DelGiorno, Jennifer M. Bailey‐Lundberg. CD73 ‐generated extracellular adenosine promotes resolution of neutrophil‐mediated tissue injury and restrains metaplasia in pancreatitis. The FASEB Journal 2023, 37 (1) https://doi.org/10.1096/fj.202201537R
    41. Daniela Catarzi, Flavia Varano, Sara Calenda, Erica Vigiani, Vittoria Colotta. Once Upon a Time Adenosine and Its Receptors: Historical Survey and Perspectives as Potential Targets for Therapy in Human Diseases. 2023, 1-46. https://doi.org/10.1007/7355_2023_158
    42. . Selective Mechanism of Inhibitors to Two Bromodomains of BRD4 Revealed by Multiple Replica Molecular Dynamics Simulations and Free Energy Analyses. Chinese Journal of Chemical Physics 2023https://doi.org/10.1063/1674-0068/cjcp2208126
    43. Minfei Su, Navid Paknejad, Lan Zhu, Jinan Wang, Hung Nguyen Do, Yinglong Miao, Wei Liu, Richard K. Hite, Xin-Yun Huang. Structures of β1-adrenergic receptor in complex with Gs and ligands of different efficacies. Nature Communications 2022, 13 (1) https://doi.org/10.1038/s41467-022-31823-1
    44. Yang Li, Jixue Sun, Dongmei Li, Jianping Lin. The full activation mechanism of the adenosine A 1 receptor revealed by GaMD and Su-GaMD simulations. Proceedings of the National Academy of Sciences 2022, 119 (42) https://doi.org/10.1073/pnas.2203702119
    45. Y.X. Yu, W. Wang, H.B. Sun, L.L. Zhang, L.F. Wang, Y.Y. Yin. Decoding drug resistant mechanism of V32I, I50V and I84V mutations of HIV-1 protease on amprenavir binding by using molecular dynamics simulations and MM-GBSA calculations. SAR and QSAR in Environmental Research 2022, 33 (10) , 805-831. https://doi.org/10.1080/1062936X.2022.2140708
    46. Berkay Selçuk, Ismail Erol, Serdar Durdağı, Ogün Adebali. Evolutionary association of receptor-wide amino acids with G protein–coupling selectivity in aminergic GPCRs. Life Science Alliance 2022, 5 (10) , e202201439. https://doi.org/10.26508/lsa.202201439
    47. Meng Li, Xinguo Liu, Shaolong Zhang, Shanshan Liang, Qinggang Zhang, Jianzhong Chen. Deciphering the binding mechanism of inhibitors of the SARS-CoV-2 main protease through multiple replica accelerated molecular dynamics simulations and free energy landscapes. Physical Chemistry Chemical Physics 2022, 24 (36) , 22129-22143. https://doi.org/10.1039/D2CP03446H
    48. Zhiping Yu, Hongyi Su, Jianzhong Chen, Guodong Hu. Deciphering Conformational Changes of the GDP-Bound NRAS Induced by Mutations G13D, Q61R, and C118S through Gaussian Accelerated Molecular Dynamic Simulations. Molecules 2022, 27 (17) , 5596. https://doi.org/10.3390/molecules27175596
    49. Jianzhong Chen, Jian Wang, Qingkai Zeng, Wei Wang, Haibo Sun, Benzheng Wei. Exploring the deactivation mechanism of human β2 adrenergic receptor by accelerated molecular dynamic simulations. Frontiers in Molecular Biosciences 2022, 9 https://doi.org/10.3389/fmolb.2022.972463
    50. Xuesong Wang, Willem Jespers, Just J. de Waal, Kim A. N. Wolff, Liedeke van Uden, Adriaan P. IJzerman, Gerard J. P. van Westen, Laura H. Heitman. Cancer‐related somatic mutations alter adenosine A 1 receptor pharmacology—A focus on mutations in the loops and C‐terminus. The FASEB Journal 2022, 36 (6) https://doi.org/10.1096/fj.202200203RR
    51. Jianzhong Chen, Shaolong Zhang, Qingkai Zeng, Wei Wang, Qinggang Zhang, Xinguo Liu. Free Energy Profiles Relating With Conformational Transition of the Switch Domains Induced by G12 Mutations in GTP-Bound KRAS. Frontiers in Molecular Biosciences 2022, 9 https://doi.org/10.3389/fmolb.2022.912518
    52. Jinan Wang, Apurba Bhattarai, Hung N. Do, Sana Akhter, Yinglong Miao. Molecular Simulations and Drug Discovery of Adenosine Receptors. Molecules 2022, 27 (7) , 2054. https://doi.org/10.3390/molecules27072054
    53. Fuhui Zhang, Yuan Yuan, Yichi Chen, Jianfang Chen, Yanzhi Guo, Xuemei Pu. Molecular insights into the allosteric coupling mechanism between an agonist and two different transducers for μ-opioid receptors. Physical Chemistry Chemical Physics 2022, 24 (9) , 5282-5293. https://doi.org/10.1039/D1CP05736G
    54. Morad Mustafa, Mohammed Gharaibeh. Most Probable Druggable Pockets in Mutant p53-Arg175His Clusters Extracted from Gaussian Accelerated Molecular Dynamics Simulations. The Protein Journal 2022, 41 (1) , 27-43. https://doi.org/10.1007/s10930-022-10041-0
    55. Congcong Li, Kaifeng Liu, Siao Chen, Lu Han, Weiwei Han. Gaussian Accelerated Molecular Dynamics Simulations Investigation on the Mechanism of Angiotensin-Converting Enzyme (ACE) C-Domain Inhibition by Dipeptides. Foods 2022, 11 (3) , 327. https://doi.org/10.3390/foods11030327
    56. Shanshan Liang, Xinguo Liu, Shaolong Zhang, Meng Li, Qinggang Zhang, Jianzhong Chen. Binding mechanism of inhibitors to SARS-CoV-2 main protease deciphered by multiple replica molecular dynamics simulations. Physical Chemistry Chemical Physics 2022, 24 (3) , 1743-1759. https://doi.org/10.1039/D1CP04361G
    57. Jianzhong Chen, Qingkai Zeng, Wei Wang, Qingquan Hu, Huayin Bao. Q61 mutant-mediated dynamics changes of the GTP-KRAS complex probed by Gaussian accelerated molecular dynamics and free energy landscapes. RSC Advances 2022, 12 (3) , 1742-1757. https://doi.org/10.1039/D1RA07936K
    58. Jinan Wang, Lan Lan, Xiaoqing Wu, Liang Xu, Yinglong Miao. Mechanism of RNA recognition by a Musashi RNA-binding protein. Current Research in Structural Biology 2022, 4 , 10-20. https://doi.org/10.1016/j.crstbi.2021.12.002
    59. Ravinder Abrol, Erik Serrano, Luis Jaimes Santiago. Development of enhanced conformational sampling methods to probe the activation landscape of GPCRs. 2022, 325-359. https://doi.org/10.1016/bs.apcsb.2021.11.001
    60. Haixia Su, Sheng Yao, Wenfeng Zhao, Yumin Zhang, Jia Liu, Qiang Shao, Qingxing Wang, Minjun Li, Hang Xie, Weijuan Shang, Changqiang Ke, Lu Feng, Xiangrui Jiang, Jingshan Shen, Gengfu Xiao, Hualiang Jiang, Leike Zhang, Yang Ye, Yechun Xu. Identification of pyrogallol as a warhead in design of covalent inhibitors for the SARS-CoV-2 3CL protease. Nature Communications 2021, 12 (1) https://doi.org/10.1038/s41467-021-23751-3
    61. Hui Zhang, Kun Chen, Qiuxiang Tan, Qiang Shao, Shuo Han, Chenhui Zhang, Cuiying Yi, Xiaojing Chu, Ya Zhu, Yechun Xu, Qiang Zhao, Beili Wu. Structural basis for chemokine recognition and receptor activation of chemokine receptor CCR5. Nature Communications 2021, 12 (1) https://doi.org/10.1038/s41467-021-24438-5
    62. Christopher J. Draper-Joyce, Rebecca Bhola, Jinan Wang, Apurba Bhattarai, Anh T. N. Nguyen, India Cowie-Kent, Kelly O’Sullivan, Ling Yeong Chia, Hariprasad Venugopal, Celine Valant, David M. Thal, Denise Wootten, Nicolas Panel, Jens Carlsson, Macdonald J. Christie, Paul J. White, Peter Scammells, Lauren T. May, Patrick M. Sexton, Radostin Danev, Yinglong Miao, Alisa Glukhova, Wendy L. Imlach, Arthur Christopoulos. Positive allosteric mechanisms of adenosine A1 receptor-mediated analgesia. Nature 2021, 597 (7877) , 571-576. https://doi.org/10.1038/s41586-021-03897-2
    63. Jinan Wang, Pablo R. Arantes, Apurba Bhattarai, Rohaine V. Hsu, Shristi Pawnikar, Yu‐ming M. Huang, Giulia Palermo, Yinglong Miao. Gaussian accelerated molecular dynamics: Principles and applications. WIREs Computational Molecular Science 2021, 11 (5) https://doi.org/10.1002/wcms.1521
    64. Carina Höring, Marcus Conrad, Christian A. Söldner, Jinan Wang, Heinrich Sticht, Andrea Strasser, Yinglong Miao. Specific Engineered G Protein Coupling to Histamine Receptors Revealed from Cellular Assay Experiments and Accelerated Molecular Dynamics Simulations. International Journal of Molecular Sciences 2021, 22 (18) , 10047. https://doi.org/10.3390/ijms221810047
    65. Jianzhong Chen, Lifei Wang, Wei Wang, Haibo Sun, Laixue Pang, Huayin Bao. Conformational transformation of switch domains in GDP/K-Ras induced by G13 mutants: An investigation through Gaussian accelerated molecular dynamics simulations and principal component analysis. Computers in Biology and Medicine 2021, 135 , 104639. https://doi.org/10.1016/j.compbiomed.2021.104639
    66. S.S. Liang, X.G. Liu, Y.X. Cui, S.L. Zhang, Q.G. Zhang, J.Z. Chen. Molecular mechanism concerning conformational changes of CDK2 mediated by binding of inhibitors using molecular dynamics simulations and principal component analysis. SAR and QSAR in Environmental Research 2021, 32 (7) , 573-594. https://doi.org/10.1080/1062936X.2021.1934896
    67. Jianzhong Chen, Wei Wang, Haibo Sun, Laixue Pang, Huayin Bao. Binding mechanism of inhibitors to p38α MAP kinase deciphered by using multiple replica Gaussian accelerated molecular dynamics and calculations of binding free energies. Computers in Biology and Medicine 2021, 134 , 104485. https://doi.org/10.1016/j.compbiomed.2021.104485
    68. Junxiao Chen, Na Li, Xingyu Wang, Jianzhong Chen, John Z. H. Zhang, Tong Zhu. Molecular mechanism related to the binding of fluorophores to Mango-II revealed by multiple-replica molecular dynamics simulations. Physical Chemistry Chemical Physics 2021, 23 (17) , 10636-10649. https://doi.org/10.1039/D0CP06438F
    69. Siyu Zhu, Meixian Wu, Ziwei Huang, Jing An. Trends in application of advancing computational approaches in GPCR ligand discovery. Experimental Biology and Medicine 2021, 246 (9) , 1011-1024. https://doi.org/10.1177/1535370221993422
    70. Hung N. Do, Sana Akhter, Yinglong Miao. Pathways and Mechanism of Caffeine Binding to Human Adenosine A2A Receptor. Frontiers in Molecular Biosciences 2021, 8 https://doi.org/10.3389/fmolb.2021.673170
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    Cite this: J. Phys. Chem. B 2019, 123, 30, 6462–6473
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    https://doi.org/10.1021/acs.jpcb.9b04867
    Published July 8, 2019
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