This website uses cookies so that we can provide the best service possible. For more information, please visit our privacy policy.
ok

sign in
|
register

scientific challenge

winter 2018 challenge launched
submit your proposal until November 23rd

news of the week

We are excited to announce that the winner of the fall 2017 challenge has been determined. Believe us, it was a tough decision! Congratulation to all contestants who provided great results and compelling summaries. In the end it was small differences that determined the winner:

Nadezhda Demina
Ural Federal University
Ekaterinburg, Russian Federation

Diabetes mellitus type 2

Dual action agent: activator of glucokinase and inhibitor of dipeptidyl peptidase-4
Nadezhda summarizes:
For 12 months of fruitful work we have been able to find out the key factor causing the pharmacological activity of the ligand, to design a molecule with potential activity for both glucokinase and a-glucosidase, and to synthesize and test this compound. In the course of our work, the two programs have become indispensable helpers: LeadIT has helped us to reveal the regularity in the ligand's manifestation of biological activity, and with the help of SeeSAR we constructed dual action agent, which was confirmed by biological tests.
The following goals have been achieved:
  1. To understand the key ligand-receptor interactions that cause pharmacological activity. This is extremely important in the development of the glucokinase activator, since the regulation of the enzyme is carried out through the allosteric center. We used LeadIT soft for docking more than 50 known glucokinase activators, as well as previously developed by us compounds with different activity against glucokinase, and compared the set of amino acids to which each of the compounds binds using 2D diagrams. This allowed us to find out that the necessary condition for an active compound is its ability to interact with Arg63 of the binding site. It was the key data for our further research.
  2. To create a molecule with potential activity for both glucokinase and a-glucosidase. No doubt the most effective tool for implementing this goal is the SeeSAR program. We sequentially built the backbone of the molecule, using two proteins as a reference point, and then modified the resulting scaffold to achieve the best affinity indices in both cases. So we were able to achieve pM affinity for glucokinase and nM one for a-glucosidase.
  3. To confirm results in practice. We synthesized 20 molecules with minor modifications of the leader compound. The assembly of the created scaffold was more complicated than we expected, and was associated with the development of new synthetic approaches. All obtained compounds were sent for biological studies. Unfortunately, at the time of writing this report, we received data only for one of the substances. The test substance showed activity superior to the reference compound in the case of glucokinase and statistically significant inhibits the a-glucosidase.

For more information please visit the hall of fame.

invitation

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.

motivation

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.

procedure

  1. To enter the winter 2018 contest, please
    submit your proposal until November 23rd 2018
  2. Based on scientific novelty, interest of target, and approach sought, we will select from all submissions the best, maximum 5 to enter the contest. Every participant will be informed of our decision by December 1st. These most promising projects will receive free fully functional licenses and support to all relevant BioSolveIT tools, valid for 3 months.
  3. After the initial 3 months the best, maximum 3 projects will receive another 9 months of free software access to BioSolveIT's entire software suite and premium support. And after 9 months, the overall best project will be rewarded with a travel grant of 1000€ to a high impact conference for a presentation of the results.