An insight from computational approach to explore novel, high-affinity phosphodiesterase 10A inhibitors for neurological disorders
Электронный научный архив УРФУ
Информация об архиве | Просмотр оригинала| Поле | Значение | |
| Заглавие |
An insight from computational approach to explore novel, high-affinity phosphodiesterase 10A inhibitors for neurological disorders
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| Автор |
Sharma, B.
Bhattacherjee, D. Zyryanov, G. V. Purohit, R. |
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| Тематика |
MOLECULAR DOCKING
PAPAVERINE PDE10A STEERED MOLECULAR DYNAMICS SIMULATIONS UMBRELLA SAMPLING SIMULATIONS CHLORIDE ION CYCLIC AMP DEPENDENT PROTEIN KINASE CYCLIC GMP PAPAVERINE PHOSPHODIESTERASE PAPAVERINE PDE10A PROTEIN, HUMAN PHOSPHODIESTERASE PHOSPHODIESTERASE INHIBITOR ABSORPTION ARTICLE BINDING AFFINITY COMPUTER MODEL CRYSTAL STRUCTURE DISTRIBUTION PARAMETERS EXCRETION HUMAN HUNTINGTON CHOREA HYDROGEN BOND METABOLISM MOLECULAR DOCKING MOLECULAR DYNAMICS MOLECULAR MECHANICS NEUROLOGIC DISEASE PARKINSON DISEASE PROTEIN CONFORMATION PROTEIN SECONDARY STRUCTURE PSYCHOSIS SCHIZOPHRENIA STATIC ELECTRICITY TOXICITY TOXICITY TESTING CHEMISTRY HUMANS MOLECULAR DOCKING SIMULATION MOLECULAR DYNAMICS SIMULATION NERVOUS SYSTEM DISEASES PAPAVERINE PHOSPHODIESTERASE INHIBITORS PHOSPHORIC DIESTER HYDROLASES |
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| Описание |
The enzyme Phosphodiesterase 10A (PDE10A) plays a regulatory role in the cAMP/protein kinase A (PKA) signaling pathway by means of hydrolyzing cAMP and cGMP. PDE10A emerges as a relevant pharmacological drug target for neurological conditions such as psychosis, schizophrenia, Parkinson's, Huntington’s disease, and other memory-related disorders. In the current study, we subjected a set of 1,2,3-triazoles to be explored as PDE10A inhibitors using diverse computational approaches, including molecular docking, classical molecular dynamics (MD) simulations, Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) calculations, steered MD, and umbrella sampling simulations. Molecular docking of cocrystallized ligands papaverine and PFJ, along with a set of in-house synthesized molecules, suggested that molecule 3i haded the highest binding affinity, followed by 3h and 3j. Furthermore, the structural stability studies using MD and MM-PBSA indicated that the 3h and 3j formed stable complexes with PDE10A. The binding free energy of −240.642 kJ/mol and −201.406 kJ/mol was observed for 3h and 3j, respectively. However, the cocrystallized ligands papaverine and PFJ exhibited comparitively higher binding free energy values of −202.030 kJ/mol and −138.764 kJ/mol, respectively. Additionally, steered MD and umbrella sampling simulations provided conclusive evidence that the molecules 3h and 3j could be exploited as promising candidates to target PDE10A. Communicated by Ramaswamy H. Sarma. © 2022 Informa UK Limited, trading as Taylor & Francis Group.
5171; Department of Biotechnology, Ministry of Science and Technology, India, DBT: DBTHRDPMU/JRF/BET-20/I/2020/AL/36; Council of Scientific and Industrial Research, India, CSIR; Ministry of Education and Science of the Russian Federation, Minobrnauka: 075-15-2020-777 The CSIR support in the form of projects MLP:0201 for bioinformatics studies is highly acknowledged. G.V.Z. acknowledge the Ministry of Science and Higher Education of the Russian Federation within the framework of the grant agreement as government subsidies from the Federal budget in accordance with paragraph 4 of article 78.1 of the Budget Code of the Russian Federation (Moscow, 1 October 2020, No. 075-15-2020-777). BS acknowledges the Department of Biotechnology, New Delhi, India for providing junior research fellowship File No: DBTHRDPMU/JRF/BET-20/I/2020/AL/36. This manuscript represents CSIR-IHBT communication no. 5171. We gratefully acknowledge to the Director, CSIR-Institute of Himalayan Bioresource Technology, Palampur for providing the facilities to carry out this work. |
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| Дата |
2024-04-05T16:17:40Z
2024-04-05T16:17:40Z 2023 |
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| Тип |
Article
Journal article (info:eu-repo/semantics/article) |info:eu-repo/semantics/submittedVersion |
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| Идентификатор |
Sharma, B, Bhattacherjee, D, Zyryanov, G & Purohit, R 2023, 'An insight from computational approach to explore novel, high-affinity phosphodiesterase 10A inhibitors for neurological disorders', Journal of Biomolecular Structure and Dynamics, Том. 41, № 19, стр. 9424-9436. https://doi.org/10.1080/07391102.2022.2141895
Sharma, B., Bhattacherjee, D., Zyryanov, G., & Purohit, R. (2023). An insight from computational approach to explore novel, high-affinity phosphodiesterase 10A inhibitors for neurological disorders. Journal of Biomolecular Structure and Dynamics, 41(19), 9424-9436. https://doi.org/10.1080/07391102.2022.2141895 0739-1102 Final All Open Access, Green https://www.scopus.com/inward/record.uri?eid=2-s2.0-85141418163&doi=10.1080%2f07391102.2022.2141895&partnerID=40&md5=efd4c61c99bc1f9a44a939d89b01c3d8 https://figshare.com/articles/journal_contribution/An_insight_from_computational_approach_to_explore_novel_high-affinity_phosphodiesterase_10A_inhibitors_for_neurological_disorders/21509934/1/files/38122536.pdf http://elar.urfu.ru/handle/10995/130281 10.1080/07391102.2022.2141895 85141418163 000879630100001 |
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| Язык |
en
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| Права |
Open access (info:eu-repo/semantics/openAccess)
cc-by https://creativecommons.org/licenses/by/4.0/ |
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| Формат |
application/pdf
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| Издатель |
Taylor and Francis Ltd.
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| Источник |
Journal of Biomolecular Structure and Dynamics
Journal of Biomolecular Structure and Dynamics |
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