Targeting Sirtuin 1 for therapeutic potential: Drug repurposing approach integrating docking and molecular dynamics simulations

被引:3
|
作者
Alrouji, Mohammed [1 ]
Alhumaydhi, Fahad A. [2 ]
Alsayari, Abdulrhman [3 ,4 ]
Sharaf, Sharaf E. [5 ]
Shafi, Sheeba [6 ]
Anwar, Saleha [7 ]
Shahwan, Moyad [8 ]
Atiya, Akhtar [3 ]
Shamsi, Anas [8 ]
机构
[1] Shaqra Univ, Coll Appl Med Sci, Dept Med Labs, Shaqra, Saudi Arabia
[2] Qassim Univ, Coll Appl Med Sci, Dept Med Labs, Buraydah, Saudi Arabia
[3] King Khalid Univ KKU, Coll Pharm, Dept Pharmacognosy, Abha, Saudi Arabia
[4] King Khalid Univ KKU, Complementary & Alternat Med Unit, Abha, Saudi Arabia
[5] Qura Univ Makkah, Coll Pharm Umm Al, Pharmaceut Chem Dept, Mecca, Saudi Arabia
[6] King Faisal Univ, Coll Appl Med Sci, Dept Nursing, Al Hasa, Saudi Arabia
[7] Jamia Millia Islamia, Ctr Interdisciplinary Res Basic Sci, New Delhi, India
[8] Ajman Univ, Ctr Med & Bioallied Hlth Sci, Ajman, U Arab Emirates
来源
PLOS ONE | 2023年 / 18卷 / 12期
关键词
INHIBITOR; DISCOVERY; MECHANISM;
D O I
10.1371/journal.pone.0293185
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Identifying novel therapeutic agents is a fundamental challenge in contemporary drug development, especially in the context of complex diseases like cancer, neurodegenerative disorders, and metabolic syndromes. Here, we present a comprehensive computational study to identify potential inhibitors of SIRT1 (Sirtuin 1), a critical protein involved in various cellular processes and disease pathways. Leveraging the concept of drug repurposing, we employed a multifaceted approach that integrates molecular docking and molecular dynamics (MD) simulations to predict the binding affinities and dynamic behavior of a diverse set of FDA-approved drugs from DrugBank against the SIRT1. Initially, compounds were shortlisted based on their binding affinities and interaction analyses to identify safe and promising binding partners for SIRT1. Among these candidates, Doxercalciferol and Timiperone emerged as potential candidates, displaying notable affinity, efficiency, and specificity towards the binding pocket of SIRT1. Extensive evaluation revealed that these identified compounds boast a range of favorable biological properties and prefer binding to the active site of SIRT1. To delve deeper into the interactions, all-atom MD simulations were conducted for 500 nanoseconds (ns). These simulations assessed the conformational dynamics, stability, and interaction mechanism of the SIRT1-Doxercalciferol and SIRT1-Timiperone complexes. The MD simulations illustrated that the SIRT1-Doxercalciferol and SIRT1-Timiperone complexes maintain stability over a 500 ns trajectory. These insightful outcomes propose that Doxercalciferol and Timiperone hold promise as viable scaffolds for developing potential SIRT1 inhibitors, with implications for tackling complex diseases such as cancer, neurodegenerative disorders, and metabolic syndromes.
引用
收藏
页数:18
相关论文
共 50 条
  • [41] DFT, FMO, ESP, Molecular Docking and Molecular Dynamics Simulations of Bis-2-(2-Phenethyl)Chromone as a Potential PPAR Agonist
    Qiu, Yingqi
    Lai, Wuji
    Feng, Yu
    Zhu, Qinghua
    Wang, Yuanmeng
    Jiang, Lihe
    Lei, Fuhou
    Shen, Liqun
    Wu, Aiqun
    LETTERS IN ORGANIC CHEMISTRY, 2023, 20 (07) : 678 - 687
  • [42] Identification of natural marine compounds as potential inhibitors of CDK2 using molecular docking and molecular dynamics simulation approach
    Ahmad, Basharat
    Saeed, Aamir
    Castrosanto, Melvin A.
    Zia, Muhammad Amir
    Farooq, Umar
    Abbas, Zaheer
    Khan, Sara
    JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS, 2023, 41 (17) : 8506 - 8516
  • [43] Screening of novel histone deacetylase 7 inhibitors through molecular docking followed by a combination of molecular dynamics simulations and ligand-based approach
    Yuan, Yuan
    Hu, Zongyue
    Bao, Minyue
    Sun, Rong
    Long, Xin
    Long, Li
    Li, Jianzong
    Wu, Chuanfang
    Bao, Jinku
    JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS, 2019, 37 (15) : 4092 - 4103
  • [44] Potential inhibitors of the enzyme acetylcholinesterase and juvenile hormone with insecticidal activity: study of the binding mode via docking and molecular dynamics simulations
    Ramos, Ryan S.
    Macedo, Williams J. C.
    Costa, Josivan S.
    da Silva, Carlos H. T. de P.
    Rosa, Joaquin M. C.
    da Cruz, Jorddy Neves
    de Oliveira, Mozaniel S.
    de Aguiar Andrade, Eloisa H.
    e Silva, Raullyan B. L.
    Souto, Raimundo N. P.
    Santos, Cleydson B. R.
    JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS, 2020, 38 (16) : 4687 - 4709
  • [45] Identification of potential Staphylococcus aureus dihydrofolate reductase inhibitors using QSAR, molecular docking, dynamics simulations and free energy calculation
    Matos, Isaac de Araujo
    Goes Pinto, Ana Carolina
    Ferraz, Matheus Vitor Ferreira
    Adan, Wenny Camilla Santos
    Rodrigues, Ricardo Pereira
    dos Santos, Juliane Xavier
    Kitagawa, Rodrigo Rezende
    Lins, Roberto Dias
    Oliveira, Tiago Branquinho
    da Costa, Nivan Bezerra, Jr.
    JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS, 2023, 41 (09) : 3835 - 3846
  • [46] Molecular docking and molecular dynamics simulation approach to screen natural compounds for inhibition of Xanthomonas oryzae pv. Oryzae by targeting peptide deformylase
    Joshi, Tushar
    Joshi, Tanuja
    Sharma, Priyanka
    Chandra, Subhash
    Pande, Veena
    JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS, 2021, 39 (03) : 823 - 840
  • [47] Design of novel DABO derivatives as HIV-1 RT inhibitors using molecular docking, molecular dynamics simulations and ADMET properties
    Zhang, Yanjun
    Chen, Lu
    Wang, Zhonghua
    Zhu, Yiren
    Jiang, Huifang
    Xu, Jie
    Xiong, Fei
    JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS, 2023, 42 (08) : 4196 - 4213
  • [48] Exploring the potential mechanisms of Mahuang Fuzi Xixin decoction in treating elderly bronchial asthma through network pharmacology, molecular docking, and molecular dynamics simulations
    Yu, Hongpeng
    Wei, Xiaotong
    Ding, Huan
    Hu, Shaodan
    Sun, Feng
    Cao, Zhenghua
    Shi, Li
    MEDICINE, 2024, 103 (41) : e39921
  • [49] Anti-HIV Potential of Beesioside I Derivatives as Maturation Inhibitors: Synthesis, 3D-QSAR, Molecular Docking and Molecular Dynamics Simulations
    Zhao, Zixuan
    Ma, Yinghong
    Li, Xiangyuan
    Morris-Natschke, Susan L.
    Sun, Zhaocui
    Sun, Zhonghao
    Ma, Guoxu
    Dong, Zhengqi
    Zhao, Xiaohong
    Yang, Meihua
    Xu, Xudong
    Lee, Kuohsiung
    Wu, Haifeng
    Chen, Chinho
    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2023, 24 (02)
  • [50] Computational design of novel flavonoid analogues as potential AChE inhibitors: analysis using group-based QSAR, molecular docking and molecular dynamics simulations
    Vats, Chakshu
    Dhanjal, Jaspreet Kaur
    Goyal, Sukriti
    Bharadvaja, Navneeta
    Grover, Abhinav
    STRUCTURAL CHEMISTRY, 2015, 26 (02) : 467 - 476