Time is running out! Only a few days left until our spring 2019 challenge's deadline to submit a project proposal (Thursday, February 21st).
Submit your proposal now if you would like to get the chance to win a €1,000 travel grant to a high impact conference, if your abstract is accepted.
If you would like to propel your project with a variety of software ranging from hit finding over SBDD, SBDD and lead optimization, you should benefit of BioSolveIT's Scientific Challenge: 3 contestants from the spring 2018, the summer 2018, and the fall 2018 challenges are currently battling over first place, and 5 contestants from the winter 2018 challenge have almost wrapped up their first phase.
We would like to see your proposal, too!
The following project won the 'winter 2017' scientific challenge:
During last 12 months, we have been working in a new project about protein-protein interactions (PPIs). We have developed the project with the computational support of Biosolveit software. Chronic kidney disease (CKD) is the nonâ€“transmissible global cause of death that raised the most within the past 20 years. It increases the risk of allâ€“cause mortality and may progress to endâ€“stage of renal failure. There is no effective therapy for CKD and current approaches do not prevent its progression. Then, the search of new and validated targets against CKD has become a milestone in academic groups and industry. CKD has been related, at least partially, to integrinâ€“linked kinase (ILK). This is an intracellular pseudokinase which forms the ternary complex IPP (ILKâ€“PINCHâ€“parvin) with two adaptor proteins. On the other hand, disrupting PPIs has emerged as a very promising strategy against different types of diseases due to its high selectivity and specifity. We have focused our efforts in disrupting the ILKâ€“parvin interaction to validate this protein as target for CKD and to get insight of the function of this complex. Our first effort was aimed to identify the hotspot of the surface of interaction in ILK. We were able to identify a hotspot, with the help of Seesar and HYDE, in a new way which agrees with other representative methods. Once we acquired this information, we prepared a set of small peptides and optimized them using ReCore in order to validate this proof of concept. As a result of the former, some of these peptides exhibited the desired activity in phenotypic assays, thus supporting our hypothesis. Next, we prepared longer peptides to get more insight onto the PPI. We used Seesar to study all the peptides resulting from an alanine scanning, and Flexx to dock all of them. Again, we used HYDE scoring function to correlate HYDE energy values with affinity values (KD) obtained by SPR experiments. These results have let to identify a peptide with good activity and a very interesting Koff value (0.691 uM), which could be used as tool in biological chemistry. Finally, we are now performing a virtual screening using ZINC database and a consensus approach to identify peptidomimetic structures. Thus, we are using HYDE as a scoring function for the best docked candidates in order to select them for further steps of virtual screening (i.e. molecular dynamics) and synthesis. Summarizing, we have proved the versatility of Biosolveit software to lead new projects in the field of PPIs never studied before. Moreover, our results will be completed by identification of small hit molecules as potential drug-like compounds able to disrupt ILK-parvin interaction.
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.