The supreme art of war is to subdue 

the enemy without fighting.

Sun Tzu

The Interview about SiDock@HOME BOINC project

Matteo:It is always good news when a new Boinc project starts, and even more so it is good news that this new project will fight the coronavirus. Nevertheless, I still have some questions before I am sure that it is worth dedicating some of my (small) hardware resources to this project.

Marko & Natalia: We are indeed grateful that you are all helping us. Each individual is the key to the success of the whole project, and we believe that shared science and/or community science is the key to the future. Successful communication between science and community is also an example of how useful information can be made available and disseminated in the community.

Matteo: It is very nice to see the face of the people working on this project on https://covid.si/en/team/. However, I wonder if this is an “independent” project run by these people or if it is affiliated with one or more academic institutes.

Marko & Natalia: Well, it was a small organic project that started with a beer between colleagues from the field of drug design and medicinal chemistry here in Slovenija. We discussed how we could help, and modestly started a small project. With time the project was born. The project grew slowly, and since we are all in academic institutions, we also received support from them. Yes, so the member organisations are the University of Maribor, the University of Ljubljana, CTK Ljubljana, the Karelian Research Center of Russian Academy of Sciences,… namely our primary institutions. However, as we work, we have an international network with which we cooperate, and we are supported by other research groups and laboratories all over the world. Namely, we are now working on getting support from synthesis and biology groups to get testing facilities on isolated proteins as well as on cell lines. In the future, we want to create produce compounds that have activity on physical systems and can serve as probes for virus research or as lead structures for drug development.                                 

Matteo: There is a very similar project to the World community grid, Open Pandemics – COVID 19 ( https://www.worldcommunitygrid.org/research/opn1/overview.do ). They are testing the database ZINC (https://zinc15.docking.org/) against several targets of the virus, and their processing power is much higher than here. Of course, redundancy in science is a good thing, but is this project in any way different or is it testing the same molecules and targets of OpenPandemics? And maybe the same as Ibercivis?”

Marko & Natalia: Yes, in science, many issues are being studied in parallel, and our project is just one of the many options proposed by the community, such as JEDI Grand Challenge (https://www.covid19.jedi.group/ ). We are not entirely familiar with the OpenPandemics and Ibercivis CORONA projects, but I think we are similar. We see that OpenPandemics has many much-needed approaches, and the Ibercivis CORONA project is also starting on a good foundation. What we can tell you with certainty is this: We are a focused group of scientists in the field of drug design, to conduct a series of scientific projects on focused targets (now it is only 3CLpro, the next target is being carefully studied). Our goal is to build ever more extensive libraries of compounds to cover novel chemical space. Our goal is to place the compounds for biological evaluation. Last but not least, we want to be transparent and collaborate with the community.

Matteo: What is RXDock? (And CurieMariedock too?) Is it open source? In what way is it different/better/worse than the well-known Autodock? 

Marko & Natalia: Molecular Docking is a complex and multifaceted problem, and there are many computational tools for this task. Autodock, Autodock VINA, Glide, Fred, DOCK, Gold are just a few examples. It is not easy to compare different solutions directly because the tool is only as useful as the system you are studying. The tools are often complementary, and you must test the tools on the system you are investigating. The story behind rxDock or rDock is written bellow.

The RiboDock program was developed from 1998 to 2006 by the software team of RiboTargets (later Vernalis (R&D) Ltd.) In 2006 the software was licensed to the University of York for maintenance and distribution under the name rDock.

In 2012 Vernalis and the University of York agreed to publish the program as open-source software. This version is developed with the support of the University of Barcelona — sourceforge.net/projects/rdock. The development of rDock came to a standstill in 2014. Since 2019 RxTx is developing a spin-off of rDock under the name rxDock (open-source). In order to implement new features, to optimise and use modern hardware, a spin-off from RxDock under the name CmDock or CurieMarie Dock will be developed from 2020 on, which is open source.

We have studied Rdock or RxDock (code update and rewrite and can be compiled on modern OS -it compiles nicely) on our research systems, and we got good results and decided to use this solution. As a reference, rDock was also successfully used in early corona research in an excellent Galaxy project. Since we are also software developers, we identified further possible software optimisations, and in order to implement new features and QOL improvements (GPU support), we decided to fork the project and create a novel CmDock platform to bring the software up to date (no pun intended :)).                                           

Matteo: What are the objectives of this project? Of course, the first goal is to find a molecule that can inhibit the replication of the virus, but is there some “additional” things that could help scientists in other ways, and even if this project will not be the project that will defeat the coronavirus? I think for example the development of new software, progress in fundamental areas of bioinformatics, consolidation of a new research group in Europe/ Eastern Europe /Russia and so forth.

Marko & Natalia: Yes, we are aiming for a lot more collateral outcomes. Firstly, the most important scientific contributions; secondly, the development and optimisation of software; thirdly, the establishment and consolidation of a drug development community and a research group to address future or other health issues. We would be very pleased to jointly address results on SARS-CoV-2, but also other medico-chemical problems in the future.

Moreover, finally, we would like to make some progress in the field of chemo- and bioinformatics and pass on our knowledge to young researchers. Yes, some of us are also working a lot on the methodology of bioinformatics; mainly on how to integrate additional quality data into HTVS, such as water data and additional exp… So joining this project would be the ultimate reward for the community and us: to bring some new insights into bioinformatics.

Matteo: What do you expect from this project? That is, what do you think will happen in 6 months – 1 year? Are you working on a publication?

Marko & Natalia: Yes, we are working on publications that are already available in our base institutions and of course on the joint project COVID. SI/SIDOCK, where we expect the first in silico publications to be available in early 21. In a year, we hope to have experimental hit compounds, collaboration in biology and an established community where we can work together to address and communicate the problems of drug design.

Matteo: Will the results be published as open science?

Marko & Natalia: Indeed, we hope to be able to contribute to OpenScience as well. We hope that we have answered your questions and thank you and all participants for your support. We hope that we will work even more in the future.