Search results for " virtual screening"

3d ligandbased virtual screening for deorphanisation of a human olfactory receptor

2008

International audience

CHA on CDK2: a way to identify the best pharmacophore model for the virtual screening of new inhibitors

2018

Cyclin-dependent kinase-2 (CDK2) is a member of serine/threonine protein kinases family. It plays an important role in the regulation events of the eukaryotic cell division cycle, especially during the G1 to S phase transition. Experimental evidences indicate that excessive expression of CDK2 should cause abnormal cell cycle regulation. Therefore, CDK2 has been considered a potential therapeutic target for cancer therapy. In this work, we used a modelling approach that incorporates flexibility based on extensive MD simulations of protein−ligand complexes into structure-based pharmacophore modeling and virtual screening to identify new CDK2 inhibitors. One-hundred and forty-nine CDK2-inhibit…

IN THE SEARCH OF LEPTIN AGONISTS AS ANTI-OBESITY DRUGS: PROTEIN/PROTEIN DOCKING, MOLECULAR DYNAMICS, AND VIRTUAL SCREENING

2012

The body weight control is a mechanism thinly regulated by several hormonal, metabolic, and nervous pathways (1). Recessive homozygous mutations in the ob/ob and db/db mouse strain cause extreme obesity. The products of the ob and db genes are leptin and its receptor, respectively. The leptin receptor is crucial for energy homeostasis and regulation of food uptake. Leptin is a 16 kDa hormone that is mainly secreted by fat cells into the bloodstream. Under normal circumstances, circulating leptin levels are proportionate to the fat body mass. Sensing of elevated leptin levels by the hypothalamic neurocircutry activates a negative feedback loop resulting in reduced food intake and increased e…

A dynamic-common pharmacophore approach to improve virtual screening. A case study on PPAR-alpha

2016

Fragment‐ and Negative Image‐Based Screening of Phosphodiesterase 10A Inhibitors

2019

A novel virtual screening methodology called fragment‐ and negative image‐based (F‐NiB) screening is introduced and tested experimentally using phosphodiesterase 10A (PDE10A) as a case study. Potent PDE10A‐specific small‐molecule inhibitors are actively sought after for their antipsychotic and neuroprotective effects. The F‐NiB combines features from both fragment‐based drug discovery and negative image‐based (NIB) screening methodologies to facilitate rational drug discovery. The selected structural parts of protein‐bound ligand(s) are seamlessly combined with the negative image of the target's ligand‐binding cavity. This cavity‐ and fragment‐based hybrid model, namely its shape and electr…