The Application of the Combination of Monte Carlo Optimization Method based QSAR Modeling and Molecular Docking in Drug Design and Development

2020 ◽  
Vol 20 (14) ◽  
pp. 1389-1402 ◽  
Author(s):  
Maja Zivkovic ◽  
Marko Zlatanovic ◽  
Nevena Zlatanovic ◽  
Mladjan Golubović ◽  
Aleksandar M. Veselinović
Keyword(s):  
Monte Carlo ◽  
Molecular Docking ◽  
Computer Calculation ◽  
Molecular Graph ◽  
Optimization Method ◽  
Docking Studies ◽  
Optimization Approach ◽  
Qsar Modeling ◽  
Monte Carlo Optimization ◽  
Molecular Docking Studies

In recent years, one of the promising approaches in the QSAR modeling Monte Carlo optimization approach as conformation independent method, has emerged. Monte Carlo optimization has proven to be a valuable tool in chemoinformatics, and this review presents its application in drug discovery and design. In this review, the basic principles and important features of these methods are discussed as well as the advantages of conformation independent optimal descriptors developed from the molecular graph and the Simplified Molecular Input Line Entry System (SMILES) notation compared to commonly used descriptors in QSAR modeling. This review presents the summary of obtained results from Monte Carlo optimization-based QSAR modeling with the further addition of molecular docking studies applied for various pharmacologically important endpoints. SMILES notation based optimal descriptors, defined as molecular fragments, identified as main contributors to the increase/ decrease of biological activity, which are used further to design compounds with targeted activity based on computer calculation, are presented. In this mini-review, research papers in which molecular docking was applied as an additional method to design molecules to validate their activity further, are summarized. These papers present a very good correlation among results obtained from Monte Carlo optimization modeling and molecular docking studies.

3D-QSAR modeling and molecular docking studies on a series of 2,5 disubstituted 1,3,4-oxadiazoles

2017 ◽  
Vol 1145 ◽  
pp. 278-284 ◽  
Author(s):  
Adib Ghaleb ◽  
Adnane Aouidate ◽  
Mounir Ghamali ◽  
Abdelouahid Sbai ◽  
Mohammed Bouachrine ◽  
...  
Keyword(s):  
Molecular Docking ◽  
3D Qsar ◽  
Docking Studies ◽  
Qsar Modeling ◽  
Molecular Docking Studies

scholarly journals 2D-QSAR Modeling and Molecular Docking Studies on 1H-Pyrazole-1-carbothioamide Derivatives as EGFR Kinase Inhibitors

ACS Omega ◽  
2020 ◽  
Vol 5 (30) ◽  
pp. 18662-18674 ◽  
Author(s):  
Tawassl T. H. Hajalsiddig ◽  
Abu Baker M. Osman ◽  
Ahmed E. M. Saeed
Keyword(s):  
Molecular Docking ◽  
Kinase Inhibitors ◽  
Docking Studies ◽  
Qsar Modeling ◽  
Molecular Docking Studies ◽  
2D Qsar ◽  
Egfr Kinase

scholarly journals Design, Synthesis, Biological Evaluation, 2D-QSAR Modeling, and Molecular Docking Studies of Novel 1H-3-Indolyl Derivatives as Significant Antioxidants

2021 ◽  
Vol 22 (19) ◽  
pp. 10396
Author(s):  
Maged A. Aziz ◽  
Wesam S. Shehab ◽  
Ahmed A. Al-Karmalawy ◽  
Ahmed F. EL-Farargy ◽  
Magda H. Abdellattif
Keyword(s):  
Antioxidant Activity ◽  
Ascorbic Acid ◽  
Molecular Docking ◽  
Sulfonic Acid ◽  
High Efficiency ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Qsar Modeling ◽  
Molecular Docking Studies ◽  
2D Qsar

Novel candidates of 3-(4-(thiophen-2-yl)-pyridin/pyran/pyrimidin/pyrazol-2-yl)-1H-indole derivatives (2–12) were designed by pairing the pyridine/pyrane/pyrimidine/pyrazole heterocycles with indole and thiophene to investigate their potential activities as (2,2′-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) inhibitors. The purpose of these derivatives’ modification is to create high-efficiency antioxidants, especially against ABTS, as a result of the efficiency of this set of key heterocycles in the inhibition of ROS. Herein, 2D QSAR modeling was performed to recommend the most promising members for further in vitro investigations. Furthermore, the pharmacological assay for antioxidant activity evaluation of the yielded indole-based heterocycles was tested against ABTS (2,2′-azinobis (3-ethylbenzothiazoline-6-sulfonic acid); by utilizing ascorbic acid as the standard. Candidate 10 showed higher antioxidant activity (IC50 = 28.23 μg/mL) than ascorbic acid itself which achieved (IC50 = 30.03 μg/mL). Moreover, molecular docking studies were performed for the newly designed and synthesized drug candidates to propose their mechanism of action as promising cytochrome c peroxidase inhibitors compared to ascorbic acid as a reference standard. Our findings could be promising in the medicinal chemistry scope for further optimization of the newly designed and synthesized compounds regarding the introduced structure-activity relationship study (SAR) in order to get a superior antioxidant lead compound in the near future.

3D QSAR Modeling and Molecular Docking Studies on a Series of Triazole Analogues as Antibacterial Agents

2018 ◽  
Vol 59 (7) ◽  
pp. 1544-1554
Author(s):  
A. Ghaleb ◽  
A. Aouidate ◽  
A. Sbai ◽  
M. Bouachrine ◽  
T. Lakhlifi
Keyword(s):  
Molecular Docking ◽  
Antibacterial Agents ◽  
3D Qsar ◽  
Docking Studies ◽  
Qsar Modeling ◽  
Molecular Docking Studies

scholarly journals Monte Carlo Method Based QSAR Modeling of Coumarin Derivates as Potent HIV‐1 Integrase Inhibitors and Molecular Docking Studies of Selected 4‐phenyl Hydroxycoumarins

2014 ◽  
Vol 31 (2) ◽  
pp. 95-103 ◽  
Author(s):  
Jovana Veselinović ◽  
Aleksandar Veselinović ◽  
Andrey Toropov ◽  
Alla Toropova ◽  
Ivana Damnjanović ◽  
...  
Keyword(s):  
Monte Carlo ◽  
Molecular Docking ◽  
Monte Carlo Method ◽  
Docking Studies ◽  
Integrase Inhibitors ◽  
Training Set ◽  
Qsar Modeling ◽  
Qsar Models ◽  
Coumarin Compounds ◽  
Hiv 1

Summary In search for new and promising coumarin compounds as HIV-1 integrase inhibitors, chemoinformatic methods like quantitative structure-activity relationships (QSAR) modeling and molecular docking have an important role since they can predict desired activity and propose molecule binding to enzyme. The aim of this study was building of QSAR models for coumarin derivatives as HIV-1 integrase inhibitors with the application of Monte Carlo method. SMILES notation was used to represent the molecular structure and for defining optimal SMILES-based descriptors. Molecular docking into rigid enzyme active site with flexible molecule was performed. Computational results indicated that this approach can satisfactorily predict the desired activity with very good statistical significance. For best built model statistical parameters were: a) 3’ Processing activity: R2=0.9980 and Q2=0.9977 for training set and R2=0.9788 for test set and b) Integration activity: R2=0.9999 and Q2=0.9998 for training set and R2= 0.9213 for test set. Built QSAR models were applied to selected 4-phenyl hydroxycoumarins for calculating desired activity and for HIV-1 integrase inhibition estimation. Additionally, molecular docking study was performed to a newly identified pocket in the HIV-1 integrase enzyme structure for determination of selected 4-phenyl hydroxycoumarins binding mode. Monte Carlo method proved to be an efficient approach to build up a robust model for estimating HIV-1 integrase inhibition of coumarin compounds. Based on QSAR and molecular docking studies, 4-phenyl hydroxycoumarins can be considered as promising model compounds for developing new HIV-1 integrase inhibitors.

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