Here is one of the projects that made it into the spring 2019 challenge:
Abdennour will be using SeeSAR, CoLibri, PepSee, LeadIT, FlexX, ReCore, HYDE, FlexS, FTrees, FTrees-FS, PoseView, REAL Space Navigator, KNIME® Interfaces, SMARTSeditor, SMARTSviewer, TorsionAnalyzer, Mona, and DoGSiteScorer.
The following project won the 'spring 2018' scientific challenge:
Since last 12 months, with the help of Biosolveit software we have identified a novel chemical scaffold which acts as a potent inhibitor of human voltage-gated Na+ ion channel Nav1.7 for the treatment of pain. Chronic pain (CP) is a disease that results from an injury or a disease that affects the somatosensory nervous system. CP is gradually becoming a serious global health problem. Approximately 10-55% of the worldâ€™s population is suffering from chronic pain. In addition, the cost of treating chronic pain is enormous, which imposes a huge burden on health budgets. Therapeutic approaches for chronic pain have limited effectiveness. As a result, physicians prescribe opioids for chronic pain, which leads to an epidemic of opioid prescription, abuse and addiction. Thus, the development of novel, effective and safe drugs for CP is still an unmet medical need. Voltage-gated sodium (Nav) channels act as molecular targets of cardiovascular and neurological disorders. It is difficult to design selective inhibitor of Nav channels because there are nine closely related isoforms (Nav1.1 - 1.9) that share high sequence identity. We are targeting the Nav1.7, which is found in the peripheral nervous system and involved in pain perception. A new class of analgesics targeting voltage-gated sodium channels (Nav) could help to treat people with CP. Before applying for the Biosolveit challenge we obtained some preliminary data, in which we have standardized molecular dynamics simulation (MDS) experiment with positive and negative control and a few docked compounds from a small compound library. Then our next objective was to screen 1.5 million compound library for identification of inhibitor for Nav1.7 with analgesics effect. We have developed this project with the computational support of Biosolveit software. In this study, we designed a protocol for the identification of isoform-selective inhibitor of Nav1.7, by utilizing the class of isoform-selective antagonist data. Initially, a similarity search was performed and the identified hits were docked into a binding site on the fourth voltage-sensor domain, VSD4. We used the FTrees tool for similarity searching and library generation, the generated library was docked in the VSD4 domain binding site using FlexX and compounds were shortlisted using a FlexX score and SeeSAR hyde scoring. Finally, the top 25 compounds were tested with MDS. On the basis of MDS RMSD plot we have narrowed down our list to 9 compounds and purchased them for in vitro and in vivo validation. These experiments have led to identify a novel compound with good activity and a very interesting IC50 value (0.74 ÂµM). With same cycle of above methods, we have started optimization of our novel lead compounds.
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.