The Cloud-HTMD project aimed to reduce costs and improve the effectiveness of the drug discovery process. The general trend is that the search for new drugs, their validation and introduction into the market is getting more and more expensive (~2.000 M EUR per drug). Although, most of the budget goes into clinical research, there is still a significant sum (40-50%) dedicated to the early discovery stage. This stage is critical as it shapes the candidate drug molecules to improve their efficacy and reduce their potential toxicity.
The clinical research can only be afforded by large pharmaceutical companies, while the early stage can be carried out by smaller entities, even academic laboratories. Nowadays, some experimental steps can be performed virtually (i.e. simulations), which drastically reduces the cost. However, those virtual experiments require expertise in preparing and carry out simulations, and, additionally, it needs expensive computational hardware. The idea behind our project was to allow any entity to predict their compounds characteristics by computational methods and only test few of them in clinical studies. If we could just reduce the number of compounds tested by a factor of two, we could reduce the cost of the early discovery stage by more than 30%, so it would save more than 300 million euros per drug (Acellera internal marketing analysis).
Thus, in this project, Acellera proposed a new integrated computational chemistry solution based on cloud computing. The objectives we wanted to achieve by recruiting an innovation associate were:
a) to develop a web-application to facilitate the use of HTMD in the cloud for biotechnology and pharmaceutical companies
b) to develop innovative medicinal chemistry protocols via a web-based and cloud-powered infrastructure.
c) to lower the existing barriers to access and use these powerful tools
We started by developing a solution to an elemental problem: parametrization of drug-like molecules, which is of outermost importance for any application in drug discovery (e.g. including small molecule or fragment screening, conformational analysis, cryptic pocket detection, etc). To obtain parameters, we needed to use quantum mechanic (QM) calculations, which are slow and expensive. There is a lack of methods to get robust parameters quickly and at low cost. So, the application developed by the innovation associate, contributed to answer this need.
Moreover, we demonstrated the use of cloud computing to accelerate the execution of biomolecular simulations. This effectively contributes to the reduction of the time invested and the cost associated to routinary steps of the drug discovery process. We estimate that the time dedicated to simulations is reduced by a factor of 100 and that the cost is considerably lower since it does not require the purchase and maintenance of expensive IT infrastructure. In the process, we have encountered difficulties to engage customers in using our tool because of security-related concerns due to the use of the cloud. Nevertheless, after extensive discussions with IT and legal departments, we managed to convince several customers, small to middle companies (than large pharmas) and nonprofit entities (e.g. universities).
As the web applications are run in the cloud with strict confidentiality, we cannot monitor specific usage or target systems, so it is hard for us to point out which is the pharmaceutical area that may benefit the most from this technology. We firmly believe that it can be useful in many areas, as molecular dynamics simulations offer an atomistic understanding (e.g protein/ligand interaction).
