Development and application of structure-based computational pipelines: design and discovery of new bioactive compounds

Nowadays, computational methods and molecular modeling have become increasingly popular, and they have been emerging into drug design and discovery pipelines. While some skepticism about such methods has been raised in the past, with the improvement in technology infrastructure and data availability, a computational approach is not only advisable but provides a significant enhancement to any field of research at reduced costs and resources. As it has always been in the history of mankind, significant advancements that were previously unimaginable always raise some concerns, and might not be "perfect" at the beginning; but nowadays such methods have demonstrated their potential multiple times, making them indispensable tools to remain competitive and to promote innovation. A variety of research questions can be addressed with these techniques, such as the investigation of the molecular mechanism upon drug candidates binding, the discovery of hit compounds against a novel target, and the prediction of the pharmacokinetic properties of compounds. Similar procedures are fully described in the annexed papers, covering a great variety of computational methods. Among the evaluated molecules, special attention has been dedicated to natural products, after extraction and characterization of active components from the corresponding species of plants (for instance, Mimosa tenuiflora and Dalbergia tonkinensis). On the other hand, the molecular mechanism of action of synthetic ligands has been studied, either as a strategy to target particular types of cancer (FTO protein antagonists), or to inhibit microorganisms' growth in the context of antimicrobial resistance (mainly against S. aureus and P. falciparum replication). The findings derived from the application of the computational pipelines have successfully tested the hypotheses and have provided valuable insights into the research projects after experimental validation. The implementation of these methodologies in routine research will impact the quality of results and the speed at which data is generated, paving the way to pioneering scientific research alongside the latest-generation technology.