Corporate Banner
Satellite Banner
Technology Networks Header
Saturday, August 30, 2014
 
Register | Sign in
Home Page > Videos > Library Design for Tackling Protein-protein Interactions: The 2P2I Approacha
  Videos

Return

Library Design for Tackling Protein-protein Interactions: The 2P2I Approacha
SELECTBIO

In the last decade, the inhibition of protein-protein interactions (PPI) has emerged from both academic and private research as a new way to modulate protein networks. Due to the implication of PPI in numerous diseases, inhibitors of these original interactions are certainly the next generation of highly innovative drugs that will reach the market. However, in silico design of such compounds still remains challenging. We have developed 2P2IDB, a hand-curated structural database dedicated to PPI with known orthosteric inhibitors. Using structural knowledge from the recent success stories our goal is to derive some common principles to help future target selection by assessing the druggability of PPI and to accelerate the process of drug discovery by improving the quality of chemical libraries dedicated to PPI. Analysis of the small molecule inhibitors present in 2P2IDB led us to propose the ‘rule-of-four’ as a guideline to characterize PPI inhibitors. Using dedicated support vector machine approaches, we have developed 2P2IHUNTER, a tool for filtering potential orthosteric PPI modulators from large collections of compounds (article under review). This innovative tool has been applied to a set of 8.3 million compounds from the “big vendors” to design several in silico PPI focused chemical libraries. Compounds corresponding to medicinally important privileged structures, identified as core structures in numerous therapeutics, were prioritized in a medicinal oriented version of the library. The library was filtered with carbon bond saturation index (Fsp3) to escape from flatland, which resulted in a structurally-diverse chemical library of 1,683 compounds. The molecules have been purchased from the providers, stored in 364-well plates and are currently tested against a standard PPI target (MDM3/P53) to evaluate their ability to enhance hit rates in general screening campaigns. The design and molecular properties of the different in silico chemical libraries and preliminary results from the experimental screening will be discussed during the presentation.

Request more information
Company product page



For access to this article, enter your email address to instantly recieve a Password Reset link.

Please enter your email address below:

Existing users please Sign In here. Don't have an account? Register Here for free access.

Don't have an account? | Register Here

Scientific News
Watching Molecules ‘Dance’ in Real Time
Trapping light at the nanoscale enables real-time monitoring of individual molecules bending and flexing may aid in our understanding of how changes within a cell can lead to diseases such as cancer.
Repressing the Repressors May Drive Tissue-Specific Cancers
Stowers scientists establish Drosophila and mammalian models to study mutations found in pediatric brain tumors.
Genetic Basis for Rabbit Domestication Revealed
Research presents key findings in the DNA make-up of the common mammal’s brain and nervous system, which determines how wild rabbits were genetically transformed to domestic rabbits.
Fighting Prostate Cancer with a Tomato-Rich Diet
New research suggests that men who eat over 10 portions of tomatoes a week have an 18% lower risk of developing prostate cancer.
Scientists Looking Across Human, Fly and Worm Genomes Find Shared Biology
Studies reveal powerful commonalities in biological activity and regulation among species.
Genetics Used to Improve Plants for Bioenergy
An upcoming genetics investigation into the symbiotic association between soil fungi and feedstock plants for bioenergy production could lead to more efficient uptake of nutrients, which would help limit the need for expensive and polluting fertilizers.
NIH to Launch Human Safety Study of Ebola Vaccine Candidate
Trial is First in Series of Accelerated Safety Studies of Ebola Vaccines.
Gut Bacteria that Protect Against Food Allergies Identified
Common gut bacteria prevent sensitization to allergens in a mouse model for peanut allergy, paving the way for probiotic therapies to treat food allergies.
Detecting and Identifying Candida Species in Blood Samples of Critically Ill Paediatric Patients
The study aimed to develop a multiplex nested PCR method to detect and identify seven Candida species in peripheral blood samples of critically ill paediatric patients.
Cancer-Fighting Drugs Might Also Stop Malaria Early
A number of compounds have been identified which could be used to fight malaria.
Scroll Up
Scroll Down
Skyscraper Banner
Skyscraper Banner
Follow TechNetcom1 on Twitter
Technology Networks Ltd. on LinkedIn
Go to LabTube.tv