Search results for "Common hits approach"
showing 2 items of 2 documents
A Definitive Pharmacophore Modelling Study on CDK2 ATP Pocket Binders: Tracing the Path of New Virtual High-Throughput Screenings
2020
Cyclin Dependent Kinases-2 (CDK2) are members of serine/threonine protein kinases family. They play an important role in the regulation events of the eukaryotic cell division cycle, especially during the G1 to S phase transition. Experimental evidence indicate that excessive expression of CDK2s should cause abnormal cell cycle regulation. Therefore, since a long time, CDK2s have been considered potential therapeutic targets for cancer therapy. In this work, onehundred and forty-nine complexes of inhibitors bound in the CDK2-ATP pocket were submitted to short MD simulations (10ns) and free energy calculation. Comparison with experimental data (K<sub>i</sub>, K<sub>d</su…
Common Hits Approach: Combining Pharmacophore Modeling and Molecular Dynamics Simulations.
2017
We present a new approach that incorporates flexibility based on extensive MD simulations of protein-ligand complexes into structure-based pharmacophore modeling and virtual screening. The approach uses the multiple coordinate sets saved during the MD simulations and generates for each frame a pharmacophore model. Pharmacophore models with the same pharmacophore features are pooled. In this way the high number of pharmacophore models that results from the MD simulation is reduced to only a few hundred representative pharmacophore models. Virtual screening runs are performed with every representative pharmacophore model; the screening results are combined and rescored to generate a single hi…