Informatica

This work introduces ALMERIA, a decision-support tool for drug discovery. It estimates compound similarities and predicts activity, considering conformation variability. The methodology spans from data preparation to model selection and optimization. Implemented using scalable software, it handles large data volumes swiftly. Experiments were conducted on a distributed computer cluster using the DUD-E database. Models were evaluated on different data partitions to assess generalization ability with new compounds. The tool demonstrates excellent performance in molecular activity prediction (ROC AUC: 0.99, 0.96, 0.87), indicating good generalization properties of the chosen data representation and modelling. Molecular conformation sensitivity is also evaluated.

Multidimensional scaling with city-block distances is considered in this paper. The technique requires optimization of an objective function which has many local minima and can be non-differentiable at minimum points. This study is aimed at developing a fast and effective global optimization algorithm spanning the whole search domain and providing good solutions. A multimodal evolutionary algorithm is used for global optimization to prevent stagnation at bad local optima. Piecewise quadratic structure of the least squares objective function with city-block distances has been exploited for local improvement. The proposed algorithm has been compared with other algorithms described in literature. Through a comprehensive computational study, it is shown that the proposed algorithm provides the best results. The algorithm with fine-tuned parameters finds the global minimum with a high probability.