Collaborative Drug Design of Plasmodium Kinase Inhibitors

Herein is reported the authors’ experiences in establishing the Scientists Against Malaria (SAM) initiative, and the strategies employed, collaboration approach and supporting infrastructure are discussed. The collaboration initially progressed kinase inhibitor design and testing against a Plasmodium falciparum kinase as an antimalarial drug target. Swiss-based Douglas Connect coordinated the SAM consortium and test case as a part of SYNERGY, an ECFP7 research project on knowledge-oriented collaboration, and developed the specifications for carrying out the collaborative drug discovery project, including experimental and computational approaches. A collaboration pool with a focus on neglected diseases research was formed from members of the existing DC communities of practice (InnovationWell and eCheminfo CoPs). It was decided to form SAM as a Virtual Organization (VO) with the goal of designing novel drug candidates against malaria. The VO, which involved nine globally distributed partner organizations, was launched in Spring 2010, from which time the work activity reported herein was operational and ongoing for a subsequent nine months. The project involved the combination of computational and laboratory investigations producing large volumes of complex data and metadata, whose interpretation for analysis and decision-making involved many challenging and nonlinear activities. This type of work activity usually requires the substantial resources and infrastructure of a pharmaceutical company. During the pilot, the VO progressed a new “green-field” drug design project from a project start through target selection and modeling, computational modeling and design of ligands, biological materials and assay preparation, through to the completion of initial experimental screening testing in the laboratory, with a budget that was small for such a large-scale endeavor. During this process, a complex support infrastructure involving SYNERGY services was designed and tested and which put many important components in place for operating such a complex VO. The system achieved was a prototype which requires further development for further VO activity in this area. As the scale of the VO activity increases, and as a stage of multiple VOs in the future is entered, the challenge of managing events, complexity and resources will become even more complex. It is believed that a proof-of-concept has been established here for collaborative practices, culture and infrastructure in the context of drug discovery. The many challenges and lessons learned from this initial VO experience will facilitate future endeavors in this collaborative initiative, and provide a framework to guide other drug discovery collaborations.