scholarly journals Molecular modelling studies of quinazolinone derivatives as MMP-13 inhibitors by QSAR, molecular docking and molecular dynamics simulations techniques

MedChemComm ◽  
2019 ◽  
Vol 10 (1) ◽  
pp. 101-115 ◽  
Author(s):  
Shanshan Huang ◽  
Kairui Feng ◽  
Yujie Ren
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Molecular Dynamics Simulations ◽  
Molecular Modelling ◽  
Molecular Modelling Studies ◽  
Qsar Models ◽  
Modelling Studies ◽  
Dynamics Simulations ◽  
Quinazolinone Derivatives

Reliable QSAR models for quinazolinones were constructed and eight novel MMP-13 inhibitors with higher predictive activity were identified.

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 modelling studies of sirtuin 2 inhibitors using three-dimensional structure–activity relationship analysis and molecular dynamics simulations

2015 ◽  
Vol 11 (3) ◽  
pp. 723-733 ◽  
Author(s):  
Yu-Chung Chuang ◽  
Ching-Hsun Chang ◽  
Jen-Tai Lin ◽  
Chia-Ning Yang
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Comfa Model ◽  
Relationship Analysis ◽  
Structure Activity ◽  
Molecular Modelling Studies ◽  
Modelling Studies ◽  
Dynamics Simulations

In this work, a CoMFA model and molecular dynamics simulations provide guidelines for drug development of SIRT2 inhibitors.

Promising inhibitors of nsp2 of CHIKV using molecular docking and temperature-dependent molecular dynamics simulations

2021 ◽  
pp. 1-9
Author(s):  
Mahendera Kumar Meena ◽  
Durgesh Kumar ◽  
Kamlesh Kumari ◽  
Nagendra Kumar Kaushik ◽  
Rammapa Venkatesh Kumar ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Molecular Dynamics Simulations ◽  
Temperature Dependent ◽  
Dynamics Simulations

scholarly journals Molecular modelling of the nucleotide-binding domain of Wilson's disease protein: location of the ATP-binding site, domain dynamics and potential effects of the major disease mutations

2004 ◽  
Vol 382 (1) ◽  
pp. 293-305 ◽  
Author(s):  
Roman G. EFREMOV ◽  
Yuri A. KOSINSKY ◽  
Dmitry E. NOLDE ◽  
Ruslan TSIVKOVSKII ◽  
Alexander S. ARSENIEV ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Molecular Modelling ◽  
Wilson’S Disease ◽  
Wilson's Disease ◽  
Binding Domain ◽  
Atp Binding ◽  
Disease Mutations ◽  
Disease Protein ◽  
Dynamics Simulations

WNDP (Wilson's disease protein) is a copper-transporting ATPase that plays an essential role in human physiology. Mutations in WNDP result in copper accumulation in tissues and cause a severe hepato-neurological disorder known as Wilson's disease. Several mutations were surmised to affect the nucleotide binding and hydrolysis by WNDP; however, how the nucleotides bind to normal and mutated WNDP remains unknown. To aid such studies, we performed the molecular modelling of the spatial structure and dynamics of the ATP-binding domain of WNDP and its interactions with ATP. The three-dimensional models of this domain in two conformations were built using the X-ray structures of the Ca2+-ATPase in the E1 and E2 states. To study the functional aspects of the models, they were subjected to long-term molecular dynamics simulations in an explicit solvent; similar calculations were performed for the ATP-binding domain of Ca2+-ATPase. In both cases, we found large-scale motions that lead to significant changes of distances between several functionally important residues. The ATP docking revealed two possible modes of ATP binding: via adenosine buried in the cleft near residues H1069, R1151 and D1164, and via phosphate moiety ‘anchored’ by H-bonds with residues in the vicinity of catalytic D1027. Furthermore, interaction of ATP with both sites occurs if they are spatially close to each other. This may be achieved after relative domain motions of the ‘closure’ type observed in molecular dynamics simulations. The results provide a framework for analysis of disease mutations and for future mutagenesis studies.

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