Computational studies to explore inhibitors against the cyclin-dependent kinase 12/13 enzyme: an insilco pharmacophore modeling, molecular docking and dynamics approach DOI
Amar N. Ghosh, Prakash C. Jha, Anu Manhas

и другие.

Journal of Biomolecular Structure and Dynamics, Год журнала: 2023, Номер unknown, С. 1 - 14

Опубликована: Окт. 10, 2023

Cancer is enlisted among the deadliest disease all over world. The cyclin-dependent kinases 12 and 13 have been identified as cell cycle regulators. They conduct transcription co-transcriptional processes by phosphorylating C-terminal of RNA polymerase-II. Inhibition CDK12 selectively presents a novel strategy to treat triple-negative breast cancer, but dual inhibitors are still lacking. Here, we report screening natural product compound class against CDK12/13 enzyme employing various in silico methods. Complexes enzymes used form common feature pharmacophore models, whereas perform receptor-based modelling on CDK13 owing availability single PDB. On conducting representative pharmacophores, drug-like screened products were shortlisted for molecular docking studies. After calculations, candidates that showed crucial interaction with simulation Five docked selected dynamics simulations free energy calculations. Based cut-off criteria one hit was inhibitor. outcome concluded ID CNP0386383 possesses properties, displays binding pocket, shows stable dynamic behaviour higher than experimentally reported inhibitor both enzymes.Communicated Ramaswamy H. Sarma.

Язык: Английский

Structure‐Based Computational Approach in Search of the Potent Molecules Targeting Phosphoglycerate Dehydrogenase (PHGDH) Enzyme for Cancer Treatment DOI

Priyanka Solanki,

Anu Manhas, Dhaval Patel

и другие.

ChemistrySelect, Год журнала: 2024, Номер 9(41)

Опубликована: Окт. 28, 2024

Abstract This work aims to target phosphoglycerate dehydrogenase (PHGDH), a promising druggable target, that is overexpressed in various types of cancer. A structure‐based approach was employed identify novel inhibitors against the enzyme. common five‐feature pharmacophore model (RRHDA) constructed using active site co‐crystalized ligands. These chemical features were responsible for showing inhibition. The generated models subsequently subjected validation method test set, receiver‐operator characteristic analysis, enrichment factor, and Güner–Henry studies. validated screening dataset natural compounds. screened unique compounds (1795) further selected interaction analysis study ligand binding affinity considering effect hydrogen bonding desolvation hydrophobic interactions contribution binding. which exhibited good efficiency pharmacokinetics pharmacodynamic study. finalized complexes simulation studies MM/PBSA‐based free energy calculations. expands possibilities development shortlisted molecules as anti‐cancer

Язык: Английский

Процитировано

0
Development of Promising CDK5 Inhibitors Using Structure‐Based Pharmacophore Modeling, Molecular Docking, and Molecular Dynamics Approach DOI
Amar N. Ghosh,

Suruchi Bhambri,

Priyanka Solanki

и другие.

ChemistrySelect, Год журнала: 2024, Номер 9(43)

Опубликована: Ноя. 1, 2024

Abstract Cancer is highlighted as one of the deadliest diseases globally, with CDK5 identified a key enzyme in cancer progression. Despite its potential therapeutic target, developing inhibitors has been challenging. We used multicomplex‐based pharmacophore modeling on complexes, identifying hydrophobic groups, hydrogen bond donors, and acceptors crucial inhibition features. Validated models were for virtual screening drug‐like natural product databases. Thereafter, screened candidates selected to study their binding pattern efficiency enzyme. Four molecules shortlisted analyzed electrostatic (ESP) energy maps. Molecular dynamic simulations free calculations docked complexes revealed stable behavior all, three (CNP0299652, CNP0362830, CNP0009633) showing higher Poisson Boltzmann surface area continuum solvation (MM‐PBSA) scores than reference. These demonstrated characteristics, amino acid interactions, favorable electron potentials ESP plots, dynamicigher energy, highlighting inhibitors.

Язык: Английский

Процитировано

0
Docking‑based virtual screening of BRD4 (BD1) inhibitors: assessment of docking methods, scoring functions and in silico molecular properties DOI Creative Commons

Junmin Dong,

Xiaohua Hao

BMC Chemistry, Год журнала: 2024, Номер 18(1)

Опубликована: Дек. 18, 2024

To enhance the accuracy of virtual screening for bromodomain-containing protein 4 (BRD4) inhibitors, two docking protocols and seven scoring functions were compared. A total 73 crystal structures BRD4 (BD1) complexes selected analysis. Firstly, was carried out using both LibDock CDOCKER methods. The protocol shown to be more effective based on root mean square deviation (RMSD) values (in Å) between positions co-crystal structures, achieving a rate 86.3%. Then, among various (LigScore1, LigScore2, PLP1, PLP2, PMF, PMF04 Ludi3), PMF showed highest correlation with inhibition constants (r2 = 0.614), while Ludi3 scored lowest 0.266). Finally, ligand descriptors from PubChem, strong > 0.5) heavy atom count found. Based these comprehensive evaluations, function emerged as best tool docking-based potential inhibitors. And molecular properties ligands also provided information future design strategies.

Язык: Английский

Процитировано

0
Meglumine-catalyzed eco-friendly synthesis of pyrazolo[3,4-b]pyridines: exploring their potential against inflammation and arthritis using in silico studies DOI
Sunita Teli, Shivani Soni, Anu Manhas

и другие.

Research on Chemical Intermediates, Год журнала: 2024, Номер unknown

Опубликована: Дек. 24, 2024

Язык: Английский

Процитировано

0
Identification of natural compound inhibitors for substrate-binding site of MTHFD2 enzyme: Insights from structure-based drug design and biomolecular simulations DOI Creative Commons

Nisarg Rana,

Priyanka Solanki,

Rukmankesh Mehra

и другие.

Chemical Physics Impact, Год журнала: 2024, Номер unknown, С. 100809 - 100809

Опубликована: Дек. 1, 2024

Язык: Английский

Процитировано

0
Computational studies to explore inhibitors against the cyclin-dependent kinase 12/13 enzyme: an insilco pharmacophore modeling, molecular docking and dynamics approach DOI
Amar N. Ghosh, Prakash C. Jha, Anu Manhas

и другие.

Journal of Biomolecular Structure and Dynamics, Год журнала: 2023, Номер unknown, С. 1 - 14

Опубликована: Окт. 10, 2023

Cancer is enlisted among the deadliest disease all over world. The cyclin-dependent kinases 12 and 13 have been identified as cell cycle regulators. They conduct transcription co-transcriptional processes by phosphorylating C-terminal of RNA polymerase-II. Inhibition CDK12 selectively presents a novel strategy to treat triple-negative breast cancer, but dual inhibitors are still lacking. Here, we report screening natural product compound class against CDK12/13 enzyme employing various in silico methods. Complexes enzymes used form common feature pharmacophore models, whereas perform receptor-based modelling on CDK13 owing availability single PDB. On conducting representative pharmacophores, drug-like screened products were shortlisted for molecular docking studies. After calculations, candidates that showed crucial interaction with simulation Five docked selected dynamics simulations free energy calculations. Based cut-off criteria one hit was inhibitor. outcome concluded ID CNP0386383 possesses properties, displays binding pocket, shows stable dynamic behaviour higher than experimentally reported inhibitor both enzymes.Communicated Ramaswamy H. Sarma.

Язык: Английский

Процитировано

1