Your browser doesn't support javascript.
loading
Discovery of putative inhibitors of human Pkd1 enzyme: Molecular docking, dynamics and simulation, QSAR, and MM/GBSA.
Nawaz, Muhammad Zohaib; Khalid, Hafiz Rameez; Shahbaz, Sabeen; Al-Ghanim, Khalid A; Pugazhendhi, Arivalagan; Zhu, Daochen.
Afiliación
  • Nawaz MZ; International Joint Laboratory on Synthetic Biology and Biomass Biorefinery, Biofuels Institute, School of Emergency Management, School of the Environment and Safety Engineering, Jiangsu University, Zhenjiang, 212013, China.
  • Khalid HR; International Joint Laboratory on Synthetic Biology and Biomass Biorefinery, Biofuels Institute, School of Emergency Management, School of the Environment and Safety Engineering, Jiangsu University, Zhenjiang, 212013, China.
  • Shahbaz S; Department of Biochemistry, University of Agriculture, Faisalabad, 38040, Pakistan.
  • Al-Ghanim KA; Department of Zoology, College of Science, King Saud University, P.O. Box 11451, Riyadh, Saudi Arabia.
  • Pugazhendhi A; School of Engineering, Lebanese American University, Byblos, Lebanon; University Centre for Research & Development, Department of Civil Engineering, Chandigarh University, Mohali, 140103, India. Electronic address: pugal.smile@gmail.com.
  • Zhu D; International Joint Laboratory on Synthetic Biology and Biomass Biorefinery, Biofuels Institute, School of Emergency Management, School of the Environment and Safety Engineering, Jiangsu University, Zhenjiang, 212013, China. Electronic address: dczhucn@hotmail.com.
Environ Res ; 257: 119336, 2024 Sep 15.
Article en En | MEDLINE | ID: mdl-38838751
ABSTRACT
Polycystic kidney disease is the most prevalent hereditary kidney disease globally and is mainly linked to the overexpression of a gene called PKD1. To date, there is no effective treatment available for polycystic kidney disease, and the practicing treatments only provide symptomatic relief. Discovery of the compounds targeting the PKD1 gene by inhibiting its expression under the disease condition could be crucial for effective drug development. In this study, a molecular docking and molecular dynamic simulation, QSAR, and MM/GBSA-based approaches were used to determine the putative inhibitors of the Pkd1 enzyme from a library of 1379 compounds. Initially, fourteen compounds were selected based on their binding affinities with the Pkd1 enzyme using MOE and AutoDock tools. The selected drugs were further investigated to explore their properties as drug candidates and the stability of their complex formation with the Pkd1 enzyme. Based on the physicochemical and ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) properties, and toxicity profiling, two compounds including olsalazine and diosmetin were selected for the downstream analysis as they demonstrated the best drug-likeness properties and highest binding affinity with Pkd1 in the docking experiment. Molecular dynamic simulation using Gromacs further confirmed the stability of olsalazine and diosmetin complexes with Pkd1 and establishing interaction through strong bonding with specific residues of protein. High biological activity and binding free energies of two complexes calculated using 3D QSAR and Schrodinger module, respectively further validated our results. Therefore, the molecular docking and dynamics simulation-based in-silico approach used in this study revealed olsalazine and diosmetin as potential drug candidates to combat polycystic kidney disease by targeting Pkd1 enzyme.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Relación Estructura-Actividad Cuantitativa / Simulación de Dinámica Molecular / Simulación del Acoplamiento Molecular Límite: Humans Idioma: En Revista: Environ Res Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Relación Estructura-Actividad Cuantitativa / Simulación de Dinámica Molecular / Simulación del Acoplamiento Molecular Límite: Humans Idioma: En Revista: Environ Res Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos