Here is one of the projects that made it into the summer 2020 challenge:
Javier will be using SeeSAR, infiniSee, PepSee, FlexX, ReCore, HYDE, PoseView, REAL Space Navigator, SMARTSeditor, Mona, and DoGSiteScorer.
The following project won the 'summer 2019' scientific challenge:
The mitochondrial protein dynamin-related protein (Drp1) has been implicated in the development of a number of neurodegenerative diseases, including Alzheimerâ€™s disease. To date, no direct small molecule inhibitors of human Drp1 have been identified. A year ago, we started this project with three "hit" compounds (OB-27, OB-37 and OB-47), from three alternate chemical classes, which interacted with Drp1 directly and inhibited its activity in cell-based assays. Using FTrees to search for compound analogues, we found 100 analogues to purchase/synthesise for each compound class. Using SeeSAR to dock and rank the compounds, we purchased 64 analogues. Surface plasmon resonance (SPR) assays showed that 19 of these compounds directly interacted with Drp1 in a dose-response manner (Kd range 3-520uM, notably 5 compound were insoluble and 13 compounds bound to SPR chip thus binding affinity could not be assessed). This gave us an adjusted hit rate (taking into consideration compounds which could not be assessed) of approx 53%. Importantly, 12 of these interacting compounds were from the same chemical class (OB-47 analogues). This result allowed us to focus our chemistry effort into this class of compounds. Using SeeSAR, we then designed 20 compounds predicted to have better activity than our lead compound, to synthesise and assay. Unfortunately, due to COVID-19, these studies have not yet been completed. In summary, BioSolveIt software assisted us in choosing compound analogues to purchase (giving an adjusted hit rate of approx 53%). The biological evaluation for these analogues led to a front runner compound series. BioSolveIT software was again used to design compounds of this series with improved activity.
For more information please visit the hall of fame.
BioSolveIT is inviting academic teams, non-profit organizations and individuals to participate in an exciting Scientific Challenge: if you are working on a drug discovery problem, take advantage of BioSolveIT's wide array of software tools to meet your goals. How to participate? Just send us a proposal for the project you'd like to advance using BioSolveIT software. We will review every proposal very carefully and award the most attractive ones. A new contest starts every three months.
In a first phase, the most promising proposals will receive free BioSolveIT licenses for 3 months to conduct the desired research. For phase II, the most interesting results are granted a free license extension by 9 months and we will sponsor the presentation of the overall best achievement with a travel grant of 1000€. For more details please read the terms of challenge.