Molecular Modeling on Berberine Derivatives toward BuChE: An Integrated Study with Quantitative Structure-Activity Relationships Models, Molecular Docking, and Molecular Dynamics Simulations

2016 ◽  
Vol 87 (5) ◽  
pp. 649-663 ◽  
Author(s):  
Jiansong Fang ◽  
Xiaocong Pang ◽  
Ping Wu ◽  
Rong Yan ◽  
Li Gao ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Molecular Modeling ◽  
Molecular Dynamics Simulations ◽  
Quantitative Structure ◽  
Structure Activity ◽  
Quantitative Structure Activity Relationships ◽  
Dynamics Simulations ◽  
Berberine Derivatives ◽  
Integrated Study

Molecular Modeling Studies of Anti-Alzheimer Agents by QSAR, Molecular Docking and Molecular Dynamics Simulations Techniques

2020 ◽  
Vol 16 (7) ◽  
pp. 903-927 ◽  
Author(s):  
Rahman Abdizadeh ◽  
Farzin Hadizadeh ◽  
Tooba Abdizadeh
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Molecular Modeling ◽  
Molecular Dynamics Simulations ◽  
Data Set ◽  
Ache Inhibitors ◽  
Modeling Studies ◽  
Qsar Models ◽  
Molecular Modeling Studies ◽  
Dynamics Simulations

Background: Acetylcholinesterase (AChE), a serine hydrolase, is an important drug target in the treatment of Alzheimer's disease (AD). Thus, novel AChE inhibitors were designed and developed as potential drug candidates, for significant therapy of AD. Objective: In this work, molecular modeling studies, including CoMFA, CoMFA-RF, CoMSIA, HQSAR and molecular docking and molecular dynamics simulations were performed on a series of AChE inhibitors to get more potent anti-Alzheimer drugs. Methods: 2D/3D-QSAR models including CoMFA, CoMFA-RF, CoMSIA, and HQSAR methods were carried out on 40 pyrimidinylthiourea derivatives as data set by the Sybylx1.2 program. Molecular docking and molecular dynamics simulations were performed using the MOE software and the Sybyl program, respectively. Partial least squares (PLS) model as descriptors was used for QSAR model generation. Results: The CoMFA (q2, 0.629; r2ncv, 0.901; r2pred, 0.773), CoMFA-RF (q2, 0.775; r2ncv, 0.910; r2pred, 0.824), CoMSIA (q2, 0.754; r2ncv, 0.919; r2pred, 0.874) and HQSAR models (q2, 0.823; r2ncv, 0.976; r2pred, 0.854) for training and test set yielded significant statistical results. Conclusion: These QSAR models were excellent, robust and had good predictive capability. Contour maps obtained from the QSAR models were validated by molecular dynamics simulationassisted molecular docking study. The resulted QSAR models could be useful for the rational design of novel potent AChE inhibitors in Alzheimer's treatment.

Molecular Modeling Approach to Investigate the Intercalation of Phthalates and Their Metabolites in DNA Macromolecules

2019 ◽  
Vol 16 (2) ◽  
pp. 373-380 ◽  
Author(s):  
Tatiane P. Rodrigues ◽  
Jorddy N. Cruz ◽  
Tiago S. Arouche ◽  
Tais S. S. Pereira ◽  
Wanessa A. Costa ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Free Energy ◽  
Molecular Docking ◽  
Molecular Modeling ◽  
Molecular Dynamics Simulations ◽  
Binding Free Energy ◽  
Van Der Waals ◽  
Genetic Material ◽  
Ligand Interaction ◽  
Dynamics Simulations

Recent studies have reported that phthalates are capable of causing mutations and other changes in the genetic material. This study aimed to investigate the molecular interactions between phthalate di(2-ethylhexyl) phthalate (DEHP) and its metabolites monobutyl phthalate (MBP) and monoethyl phthalate (MEP), interacting with DNA. The research was conducted using molecular modeling techniques such as molecular docking and molecular dynamics simulations. Molecular docking revealed that the DEHP, MBP, and MEP are able to establish hydrogen interactions with various nucleotide bases. Molecular dynamics simulations revealed that these molecules interacted with the DNA, and the binding free energy results demonstrated that the DNA-ligand interaction has favorable free energy. The values for free binding energy were as follows: DNA–DEHP, –21.66 kcal/mol; DNA–MBP, –17.29 kcal/mol; and DNA–MEP, –20.13 kcal/mol. For these three systems, the contributions of van der Waals, electrostatic, and nonpolar solvation energy were favorable for the interaction. The van der Waals interactions contributed the major energy to the intercalation of the binders.

Molecular modeling studies to characterize N-phenylpyrimidin-2-amine selectivity for CDK2 and CDK4 through 3D-QSAR and molecular dynamics simulations

2016 ◽  
Vol 12 (4) ◽  
pp. 1250-1268 ◽  
Author(s):  
Tahir Ali Chohan ◽  
Jiong-Jiong Chen ◽  
Hai-Yan Qian ◽  
You-Lu Pan ◽  
Jian-Zhong Chen
Keyword(s):  
Molecular Dynamics ◽  
Molecular Modeling ◽  
Molecular Dynamics Simulations ◽  
3D Qsar ◽  
Structure Activity ◽  
Modeling Studies ◽  
Molecular Modeling Studies ◽  
Dynamics Simulations

Molecular modeling simulations were carried out to understand the structure–activity and selectivity correlation of N-phenylpyrimidin-2-amines binding to CDK2 and CDK4.

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