Delineating the conformational landscape and intrinsic properties of the angiotensin II type 2 receptor using a computational study

Cong, Xiaoliang; Zhang, Xiaogang; Liang, Xuefang; He, Xinheng; Tang, Yanchao; Zheng, Xing; Lu, Shaoyong; Zhang, Jiayou; Chen, Ting

doi:10.1016/j.csbj.2022.05.012

Cited by 4 publications

(2 citation statements)

References 86 publications

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“…GPCRs comprise five main families in mammals [53]. The largest is the rhodopsin family, i.e., class A, with about 284 members in humans, followed by the aGPCR family, with 33 members, and then the glutamate family (class C), secretin family (class B), and frizzled family, with 22, 15, and 11 members, respectively [54]. GPR97 is a member of the aGPCR family, expressed in human granulocytes and endothelial cells of the vasculature.…”

Section: Discussionmentioning

confidence: 99%

Mechanistic Understanding of the Palmitoylation of Go Protein in the Allosteric Regulation of Adhesion Receptor GPR97

et al. 2022

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Adhesion G-protein-coupled receptors (aGPCRs)—a major family of GPCRs—play critical roles in the regulation of tissue development and cancer progression. The orphan receptor GPR97, activated by glucocorticoid stress hormones, is a prototypical aGPCR. Although it has been established that the palmitoylation of the C-terminal Go protein is essential for Go’s efficient engagement with the active GPR97, the detailed allosteric mechanism remains to be clarified. Hence, we performed extensive large-scale molecular dynamics (MD) simulations of the GPR97−Go complex in the presence or absence of Go palmitoylation. The conformational landscapes analyzed by Markov state models revealed that the overall conformation of GPR97 is preferred to be fully active when interacting with palmitoylated Go protein. Structural and energetic analyses indicated that the palmitoylation of Go can allosterically stabilize the critical residues in the ligand-binding pocket of GPR97 and increase the affinity of the ligand for GPR97. Furthermore, the community network analysis suggests that the palmitoylation of Go not only allosterically strengthens the internal interactions between Gαo and Gβγ, but also enhances the coupling between Go and GPR97. Our study provides mechanistic insights into the regulation of aGPCRs via post-translational modifications of the Go protein, and offers guidance for future drug design of aGPCRs.

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Section: Discussionmentioning

confidence: 99%

Mechanistic Understanding of the Palmitoylation of Go Protein in the Allosteric Regulation of Adhesion Receptor GPR97

et al. 2022

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“…56 The hypothesis is that the enzyme and substrate have a strict complementary structure like a key inserted into a lock, and that both the small molecule and the substrate are rigid and immutable. However, as experiments proceed, more and more experimental data show that the receptor and small-molecule conformations are not fixed when the receptor is combined with the small molecule, [57][58][59][60][61] but rather through the role of 'induced fit', which is the 'induced-fit theory' proposed by Koshland 62 . This theory suggests that the binding of receptors to small molecules is a dynamic fit, in which the receptor is induced by the small molecule when in close proximity to it, and the receptor's conformation changes in favor of binding to the small molecule.…”

Section: Principle Of Molecular Dockingmentioning

confidence: 99%

Applying molecular docking to pesticides

Hou,

Bai,

et al. 2023

Pest Management Science

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Pesticide creation is related to sustainable agricultural development and ecological safety, and molecular docking technology can effectively help pesticide innovation. This paper introduces the basic theory of molecular docking, pesticide databases, and docking software. It also summarizes the applications of molecular docking in the field of pesticides, including virtual screening of lead compounds, detection of pesticides and their metabolites in the environment, reverse screening of pesticide targets, and the study of resistance mechanisms. Finally, the problems of molecular docking technology in the process of pesticide creation are discussed, and the prospects of molecular docking technology in the future application of new pesticide development are foreseen.This article is protected by copyright. All rights reserved.

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Hinge region mediates signal transmission of luteinizing hormone and chorionic gonadotropin receptor

Duan

et al. 2022

Computational and Structural Biotechnology Journal

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Delineating the conformational landscape and intrinsic properties of the angiotensin II type 2 receptor using a computational study

Cited by 4 publications

References 86 publications

Mechanistic Understanding of the Palmitoylation of Go Protein in the Allosteric Regulation of Adhesion Receptor GPR97

Mechanistic Understanding of the Palmitoylation of Go Protein in the Allosteric Regulation of Adhesion Receptor GPR97

Applying molecular docking to pesticides

Hinge region mediates signal transmission of luteinizing hormone and chorionic gonadotropin receptor

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