DbaitTherap

Since 2000, the rapid growth of structural data (from 10 000 structures in 2000 to 64 000 now) are at the origin of several success stories in the study of complex biological systems and in the discovery of new drugs by computer design. The analysis and comparison of structures give the chemical basis which allow to identify and design interactions with ligands. Nevertheless, most of the existing tools can only compare structures on a global analogy basis (tertiary structure), which does not always gives an explanation to observed functional differences. In this project, BIONEXT S.A., in collaboration with high-level academics, propose to develop, enhance and give the experimental proofs of the virtual screening processes based on the comparison of structural regions. This novel description of molecular structures in contiguous regions allows to identify the fine differences between binding sites and to explain why chemically near molecules may not share a same function, while chemically different molecules can share a same function. The screening of molecular regions gives several advantages: (1) regions are the smallest functional units of molecules; (2) it is possible to retrieve all the molecules that share a functional region, independantly of their size or sequence similarity or secondary or tertiary structures; (3) it becomes possible to retrieve molecular partners (proteins and RNA included) by looking for molecules that possess complementary regions; (4) the identification of a « structural code » from these regions allows to characterise functionally a molecule from its structure only by localisaing its binding sites and associated partners. The concretization of this project will lead to a new way of performing molecular analysis and to the marketing of innovative solutions answering major issues of academic and industrials, such as: (1) what is the specificity (the frequency) of a molecular region in a cellular context (problem of efficacity in drug design); (2) what are the molecular targets of a compound (molecular mechanisms of drugs); (3) what are the molecular causes of some toxicity (REACH reglementation).