scholarly journals Targeted Molecular Dynamics to determine Focal Adhesion Targeting Domain Folding Intermediates

2017 ◽  
Vol 1 (Special Issue) ◽  
pp. 27-27
Author(s):  
Pallavi Mohanty ◽  
Sonika Bhatnagar
Keyword(s):  
Molecular Dynamics ◽  
Focal Adhesion ◽  
Folding Intermediates ◽  
Targeted Molecular Dynamics

scholarly journals Qualitative Prediction of Ligand Dissociation Kinetics from Focal Adhesion Kinase Using Steered Molecular Dynamics

Life ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 74
Author(s):  
Justin Spiriti ◽  
Chung F. Wong
Keyword(s):  
Molecular Dynamics ◽  
Drug Discovery ◽  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Early Stage ◽  
Steered Molecular Dynamics ◽  
Drug Binding ◽  
Binding Kinetics ◽  
Dissociation Kinetics ◽  
Binding Characteristics

Most early-stage drug discovery projects focus on equilibrium binding affinity to the target alongside selectivity and other pharmaceutical properties. Since many approved drugs have nonequilibrium binding characteristics, there has been increasing interest in optimizing binding kinetics early in the drug discovery process. As focal adhesion kinase (FAK) is an important drug target, we examine whether steered molecular dynamics (SMD) can be useful for identifying drug candidates with the desired drug-binding kinetics. In simulating the dissociation of 14 ligands from FAK, we find an empirical power–law relationship between the simulated time needed for ligand unbinding and the experimental rate constant for dissociation, with a strong correlation depending on the SMD force used. To improve predictions, we further develop regression models connecting experimental dissociation rate with various structural and energetic quantities derived from the simulations. These models can be used to predict dissociation rates from FAK for related compounds.

Targeted molecular dynamics (TMD) of the full-length KcsA potassium channel: on the role of the cytoplasmic domain in the opening process

2013 ◽  
Vol 19 (4) ◽  
pp. 1651-1666 ◽  
Author(s):  
Yan Li ◽  
Florent Barbault ◽  
Michel Delamar ◽  
Ruisheng Zhang ◽  
Rongjing Hu
Keyword(s):  
Molecular Dynamics ◽  
Potassium Channel ◽  
Cytoplasmic Domain ◽  
Full Length ◽  
Targeted Molecular Dynamics ◽  
Kcsa Potassium Channel ◽  
Opening Process

scholarly journals The Transition between the B and Z Conformations of DNA Investigated by Targeted Molecular Dynamics Simulations with Explicit Solvation

2006 ◽  
Vol 91 (8) ◽  
pp. 2976-2990 ◽  
Author(s):  
Mika A. Kastenholz ◽  
Thomas U. Schwartz ◽  
Philippe H. Hünenberger
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Targeted Molecular Dynamics ◽  
Dynamics Simulations ◽  
Explicit Solvation

scholarly journals Molecular Dynamics of A Biglycan-Rosmarinic Acid Complex with Focal Adhesion Kinase for Possible Arrest of Metastasis in Non-Small Cell Lung Cancer (NSCLC): An In- Silico Study

2019 ◽  
Vol 9 (4-A) ◽  
pp. 159-166
Author(s):  
Hyacinth Highland ◽  
Monica Thakur ◽  
Pujan Pandya ◽  
Archana Mankad ◽  
Linz-Buoy George
Keyword(s):  
Lung Cancer ◽  
Molecular Dynamics ◽  
Molecular Docking ◽  
Small Cell Lung Cancer ◽  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Cell Lung Cancer ◽  
Rosmarinic Acid ◽  
Small Cell ◽  
Small Cell Lung

Background: Non-small cell lung cancer (NSCLC) is the major cause of mortality all over the world. Significant increase of biglycan is seen in the lung cancer cells when compared with the normal cells. It promotes tumor invasion and metastasis by activating Focal Adhesion Kinase (FAK) signaling pathway. The increased FAK activity may contribute to the metastatic potential of malignant tumors. This study was carried out to establish binding interactions of some selected phytocomponents against biglycan for the possible arrest of metastasis. Methods: Protein-ligand interaction studies were performed using 30 natural compounds from different culinary herbs having potential therapeutic role against the target protein biglycan (BGN). Molegro Virtual Docker (v 5.0) was used as docking tool to evaluate the effectiveness of selected phytocomponents based upon the interaction with the protein’s active site residues with minimal binding energy. Protein-protein docking was performed to observe the interaction of BGN and FAK using Hex (v 8.0.0). Molecular dynamics (10 ns) of BGN-RA-FAK and FAK-RA-BGN was performed in Yasara structure (v 17.8.15) which showed stability of the structure in terms of RMSD values. Results: Molecular docking analysis revealed the selectivity of Rosmarinic acid (RA) towards BGN and FAK. Molecular dynamics trajectory of BGN-RA-FAK and FAK-RA-BGN complexes showed the stability of structure in terms of Time vs Energy and Time vs RMSD values and revealed that binding of RA to BGN will block the interaction of FAK. Conclusions: Hence, investigating the binding interactions of BGN-RA-FAK complex may turn out to be helpful in arresting metastasis in NSCLC. Keywords: Non-small cell lung cancer, Biglycan, Focal adhesion kinase, Phytocomponents, Molecular Docking, Molecular Dynamics

Extracting ligands from receptors by reversed targeted molecular dynamics

2015 ◽  
Vol 29 (11) ◽  
pp. 1025-1034 ◽  
Author(s):  
Romain M. Wolf
Keyword(s):  
Molecular Dynamics ◽  
Targeted Molecular Dynamics
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