scholarly journals 3D QSAR Pharmacophore Modeling, in Silico Screening, and Density Functional Theory (DFT) Approaches for Identification of Human Chymase Inhibitors

2011 ◽  
Vol 12 (12) ◽  
pp. 9236-9264 ◽  
Author(s):  
Mahreen Arooj ◽  
Sundarapandian Thangapandian ◽  
Shalini John ◽  
Swan Hwang ◽  
Jong Keun Park ◽  
...  
Keyword(s):  
Density Functional Theory ◽  
In Silico ◽  
Density Functional ◽  
3D Qsar ◽  
Pharmacophore Modeling ◽  
In Silico Screening ◽  
Functional Theory

In Silico Alkaline Hydrolysis of Octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine: Density Functional Theory Investigation

2016 ◽  
Vol 50 (18) ◽  
pp. 10039-10046 ◽  
Author(s):  
Liudmyla K. Sviatenko ◽  
Leonid Gorb ◽  
Frances C. Hill ◽  
Danuta Leszczynska ◽  
Manoj K. Shukla ◽  
...  
Keyword(s):  
Density Functional Theory ◽  
Alkaline Hydrolysis ◽  
In Silico ◽  
Density Functional ◽  
Functional Theory ◽  
Hydrolysis Of

Identification of Hydroxamic Acid Based Selective HDAC1 Inhibitors: Computer Aided Drug Design Studies

2019 ◽  
Vol 15 (2) ◽  
pp. 145-166 ◽  
Author(s):  
Preeti Patel ◽  
Vijay K. Patel ◽  
Avineesh Singh ◽  
Talha Jawaid ◽  
Mehnaz Kamal ◽  
...  
Keyword(s):  
Density Functional Theory ◽  
Hydroxamic Acid ◽  
Density Functional ◽  
Research Work ◽  
3D Qsar ◽  
Partial Least Square ◽  
Tumour Suppressor ◽  
Tumour Suppressor Genes ◽  
Functional Theory ◽  
Suppressor Genes

Background: Overexpression of Histone deacetylase 1 (HDAC1) is responsible for carcinogenesis by promoting epigenetic silence of tumour suppressor genes. Thus, HDAC1 inhibitors have emerged as the potential therapeutic leads against multiple human cancers, as they can block the activity of particular HDACs, renovate the expression of several tumour suppressor genes and bring about cell differentiation, cell cycle arrest and apoptosis. Methods: The present research work comprises atom-based 3D-QSAR, docking, molecular dynamic simulations and DFT (density functional theory) studies on a diverse series of hydroxamic acid derivatives as selective HDAC1 inhibitors. Two pharmacophoric models were generated and validated by calculating the enrichment factors with the help of the decoy set. The Four different 3D-QSAR models i.e., PLS (partial least square) model, MLR (multiple linear regression) model, Field-based model and GFA (Genetic function approximation) model were developed using ‘PHASE’ v3.4 (Schrödinger) and Discovery Studio (DS) 4.1 software and validated using different statistical parameters like internal and external validation. Results and Discussion: The results showed that the best PLS model has R2=0.991 and Q2=0.787, the best MLR model has R2= 0.993 and Q2= 0.893, the best Field-based model has R2= 0.974 and Q2= 0.782 and the best GFA model has R2= 0.868 and Q2= 0.782. Cross-validated coefficients, (rcv 2) of 0.967, 0.926, 0.966 and 0.829 was found for PLS model, MLR, Field based and GFA model, respectively, indicated the satisfactory correlativity and prediction. The docking studies were accomplished to find out the conformations of the molecules and their essential binding interactions with the target protein. The trustworthiness of the docking results was further confirmed by molecular dynamics (MD) simulations studies. Density Functional Theory (DFT) study was performed which promptly optimizes the geometry, stability and reactivity of the molecule during receptor-ligand interaction. Conclusion: Thus, the present research work provides spatial fingerprints which would be beneficial for the development of potent HDAC1 inhibitors.

In Silico Functional and Structural Insight of Prenylated Pyrazolocurcumin Derivative Associated with the PGE2 Inhibition through mPGES-1 Blocking

2021 ◽  
Vol 1025 ◽  
pp. 219-223
Author(s):  
Mohd Fadhlizil Fasihi Mohd Aluwi ◽  
Fatimah Salim ◽  
A.K.M. Moyeenul Huq ◽  
Kamal Rullah ◽  
Lam Kok Wai
Keyword(s):  
In Silico ◽  
Density Functional ◽  
Molecular Conformation ◽  
Computational Modelling ◽  
3D Qsar ◽  
Functional Theory ◽  
Modelling Studies ◽  
Structural Insight ◽  
Lead Inhibitors ◽  
Shed Light

The search of novel mPGES-1 lead inhibitors has recently become subject of interest to medicinal chemists due to the safety in comparison to existing NSAIDs such as coxibs drugs. The recent published work revealed that prenylated pyrazolocurcumin derivative as mPGES-1 has been sucessfully designed and synthesized through computational guided 3D-QSAR approach. To improve our understanding, the present paper aimed to develop in silico functional and structural insight of the compound including pharmacophore mapping, molecular electrostatic potential (MEP) simulation using Density Functional Theory (DFT) and druglikeness prediction associated with PGE2 suppression through mPGES-1 blocking. The data collected from computational modelling studies provide important insight on the molecular conformation and further shed light towards structural modification of the future novel mPGES-1 inhibitors.

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