Informative Library Design as an Efficient Strategy to Identify and Optimize Leads:  Application to Cyclin-Dependent Kinase 2 Antagonists

2003 ◽  
Vol 46 (20) ◽  
pp. 4360-4364 ◽  
Author(s):  
Erin K. Bradley ◽  
Jennifer L. Miller ◽  
Eddine Saiah ◽  
Peter D. J. Grootenhuis
Keyword(s):  
Cyclin Dependent Kinase ◽  
Library Design ◽  
Efficient Strategy

Hypoxic preconditioning reduces expression of the cyclin dependent kinase 5 in the post-ischemic neurons

2005 ◽  
Vol 25 (1_suppl) ◽  
pp. S309-S309
Author(s):  
Svetlana Pundik ◽  
W David Lust ◽  
Jose Valerio ◽  
Michael Buczek ◽  
Randall D York ◽  
...  
Keyword(s):  
Hypoxic Preconditioning ◽  
Cyclin Dependent Kinase ◽  
Cyclin Dependent Kinase 5

Cyclin dependent kinase 4 as promising drug target in adrenocortical carcinoma

2019 ◽  
Author(s):  
Raimunde Liang ◽  
Isabel Weigand ◽  
Silviu Sbiera ◽  
Stefan Kircher ◽  
Juliane Lippert ◽  
...  
Keyword(s):  
Adrenocortical Carcinoma ◽  
Drug Target ◽  
Cyclin Dependent Kinase

Homology Modeling of Mus Musculus CDK5 and Molecular Docking Studies with Flavonoids

2017 ◽  
Vol 9 (6) ◽  
Author(s):  
Sowmya Suri ◽  
Rumana Waseem ◽  
Seshagiri Bandi ◽  
Sania Shaik
Keyword(s):  
Molecular Docking ◽  
3D Model ◽  
Structural Features ◽  
Docking Studies ◽  
Amino Acid Residues ◽  
Cyclin Dependent Kinase ◽  
Ligand Complex ◽  
Ligand Interaction ◽  
Molecular Docking Studies ◽  
Cyclin Dependent Kinase 5

A 3D model of Cyclin-dependent kinase 5 (CDK5) (Accession Number: Q543f6) is generated based on crystal structure of P. falciparum PFPK5-indirubin-5-sulphonate ligand complex (PDB ID: 1V0O) at 2.30 Å resolution was used as template. Protein-ligand interaction studies were performed with flavonoids to explore structural features and binding mechanism of flavonoids as CDK5 (Cyclin-dependent kinase 5) inhibitors. The modelled structure was selected on the basis of least modeler objective function. The model was validated by PROCHECK. The predicted 3D model is reliable with 93.0% of amino acid residues in core region of the Ramachandran plot. Molecular docking studies with flavonoids viz., Diosmetin, Eriodictyol, Fortuneletin, Apigenin, Ayanin, Baicalein, Chrysoeriol and Chrysosplenol-D with modelled protein indicate that Diosmetin is the best inhibitor containing docking score of -8.23 kcal/mol. Cys83, Lys89, Asp84. The compound Diosmetin shows interactions with Cys83, Lys89, and Asp84.

A Memory-efficient Strategy for the FDTD Implementation Applied to the Photonic Crystals Problems

PIERS Online ◽  
2007 ◽  
Vol 3 (4) ◽  
pp. 374-378 ◽  
Author(s):  
Yu Liu ◽  
Ziqiang Yang ◽  
Zheng Liang ◽  
Limei Qi
Keyword(s):  
Photonic Crystals ◽  
Efficient Strategy ◽  
Memory Efficient

Reaction-based Enumeration, Active Learning, and Free Energy Calculations to Rapidly Explore Synthetically Tractable Chemical Space and Optimize Potency of Cyclin Dependent Kinase 2 Inhibitors

2019 ◽  
Author(s):  
Kyle Konze ◽  
Pieter Bos ◽  
Markus Dahlgren ◽  
Karl Leswing ◽  
Ivan Tubert-Brohman ◽  
...  
Keyword(s):  
Free Energy ◽  
Drug Discovery ◽  
Active Learning ◽  
Large Scale ◽  
Chemical Space ◽  
Population Based ◽  
Free Energy Calculations ◽  
Computational Technique ◽  
Cyclin Dependent Kinase ◽  
Energy Calculations

We report a new computational technique, PathFinder, that uses retrosynthetic analysis followed by combinatorial synthesis to generate novel compounds in synthetically accessible chemical space. Coupling PathFinder with active learning and cloud-based free energy calculations allows for large-scale potency predictions of compounds on a timescale that impacts drug discovery. The process is further accelerated by using a combination of population-based statistics and active learning techniques. Using this approach, we rapidly optimized R-groups and core hops for inhibitors of cyclin-dependent kinase 2. We explored greater than 300 thousand ideas and identified 35 ligands with diverse commercially available R-groups and a predicted IC<sub>50</sub> < 100 nM, and four unique cores with a predicted IC<sub>50</sub> < 100 nM. The rapid turnaround time, and scale of chemical exploration, suggests that this is a useful approach to accelerate the discovery of novel chemical matter in drug discovery campaigns.

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