Machine Learning Scoring Functions for Drug Discovery from Experimental and Computer-Generated Protein-Ligand Structures: Towards Per-Target Scoring Functions.

In recent years, machine learning has been proposed as a promising strategy to build accurate scoring functions for computational docking finalized to numerically empowered drug discovery. However, the latest studies have suggested that over-optimistic results had been reported due to the correlations present in the experimental databases used for training and testing. Here, we investigate the performance of an artificial neural network in binding affinity predictions, comparing results obtained using both experimental protein-ligand structures as well as larger sets of computer-generated structures created using commercial software. Interestingly, similar performances are obtained on both databases. We find a noticeable performance suppression when moving from random horizontal tests to vertical tests performed on target proteins not included in the training data. The possibility to train the network on relatively easily created computer-generated databases leads us to explore per-target scoring functions, trained and tested ad-hoc on complexes including only one target protein. Encouraging results are obtained, depending on the type of protein being addressed.

Artificial Intelligence in Evaluation of Permanent Impairment: New Operational Frontiers.

Artificial intelligence (AI) and machine learning (ML) span multiple disciplines, including the medico-legal sciences, also with reference to the concept of disease and disability. In this context, the International Classification of Diseases, Injuries, and Causes of Death (ICD) is a standard for the classification of diseases and related problems developed by the World Health Organization (WHO), and it represents a valid tool for statistical and epidemiological studies. Indeed, the International Classification of Functioning, Disability, and Health (ICF) is outlined as a classification that aims to describe the state of health of people in relation to their existential spheres (social, family, work). This paper lays the foundations for proposing an operating model for the use of AI in the assessment of impairments with the aim of making the information system as homogeneous as possible, starting from the main coding systems of the reference pathologies and functional damages. Providing a scientific basis for the understanding and study of health, as well as establishing a common language for the assessment of disability in its various meanings through AI systems, will allow for the improvement and standardization of communication between the various expert users.