Moleculaire modeling tools ter bevordering en uitbreiding van computationeel onderzoek op synthetische nucleïnezuren

Xenobiotic nucleic acids (XNAs) are chemical analogues of natural nucleic acids, modified in at least one of their three main chemical moieties: nucleobase, sugar and phosphate backbone. As analogues of natural DNA and RNA with increased biological activity, they have diverse applications that are traditionally categorized according to their mechanism of action whether they interact directly with the cellular nucleic acid, as antisense or RNAi ONs, or have their own specific structure and function, as ribozymes and aptamers. While the chemical biology side of the field has enjoyed decades worth of experimental research, the computational aspect is left to trail behind the advances made in the laboratory. The key issues are the lack of determined structures, which impact the amount of knowledge we can gather on the behaviour of these synthetic analogs. With this project, we want to devise a way to generate data from a pure in silico vantage point where we can predict the various conformational states of sugar analogs and condense that information into a force field, with which we can produce accurate models through molecular modeling. New software tools will be needed to accomodate the pipeline, to ensure a smooth process. A model builder, which is user-extensible, should provide the field of in silico XNA with the means to generate any type of nucleotide modification. A full computational pipeline should be provide the field with the ability to carry out solid, statistical predictions on nucleic acid structures, propelling the status of XNA modeling to a higher level.