MOTIVATION: With the development of sequencing techniques, the discovery of new proteins significantly exceeds the human capacity and resources for experimentally characterizing protein functions. Localization, EC numbers, and GO terms with the structure-based Cutoff Scanning Matrix (LEGO-CSM) is a comprehensive web-based resource that fills this gap by leveraging the well-established and robust graph-based signatures to supervised learning models using both protein sequence and structure information to accurately model protein function in terms of Subcellular Localization, Enzyme Commission (EC) numbers, and Gene Ontology (GO) terms. RESULTS: We show our models perform as well as or better than alternative approaches, achieving area under the receiver operating characteristic curve of up to 0.93 for subcellular localization, up to 0.93 for EC, and up to 0.81 for GO terms on independent blind tests. AVAILABILITY AND IMPLEMENTATION: LEGO-CSM's web server is freely available at https://biosig.lab.uq.edu.au/lego_csm. In addition, all datasets used to train and test LEGO-CSM's models can be downloaded at https://biosig.lab.uq.edu.au/lego_csm/data.

Drug discovery is a lengthy, costly and high-risk endeavour that is further convoluted by high attrition rates in later development stages. Toxicity has been one of the main causes of failure during clinical trials, increasing drug development time and costs. To facilitate early identification and optimisation of toxicity profiles, several computational tools emerged aiming at improving success rates by timely pre-screening drug candidates. Despite these efforts, there is an increasing demand for platforms capable of assessing both environmental as well as human-based toxicity properties at large scale. Here, we present toxCSM, a comprehensive computational platform for the study and optimisation of toxicity profiles of small molecules. toxCSM leverages on the well-established concepts of graph-based signatures, molecular descriptors and similarity scores to develop 36 models for predicting a range of toxicity properties, which can assist in developing safer drugs and agrochemicals. toxCSM achieved an Area Under the Receiver Operating Characteristic (ROC) Curve (AUC) of up to 0.99 and Pearson's correlation coefficients of up to 0.94 on 10-fold cross-validation, with comparable performance on blind test sets, outperforming all alternative methods. toxCSM is freely available as a user-friendly web server and API at http://biosig.lab.uq.edu.au/toxcsm.