SUMMARY: Sequence homology is a basic concept in protein evolution, structure and function studies. However, there are not many different tools and services for homology searches being sensitive, accurate and fast at the same time. We present a new web server for protein analysis based on COMER2, a sequence alignment and homology search method that exhibits these characteristics. COMER2 has been upgraded since its last publication to improve its alignment quality and ease of use. We demonstrate how the user can benefit from using it by providing examples of extensive annotation of proteins of unknown function. Among the distinctive features of the web server is the user's ability to submit multiple queries with one click of a button. This and other features allow for transparently running homology searches-in a command-line, programmatic or graphical environment-across multiple databases with multiple queries. They also promote extensive simultaneous protein analysis at the sequence, structure and function levels. AVAILABILITY AND IMPLEMENTATION: The COMER web server is available at https://bioinformatics.lt/comer. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Motivation: Understanding the relationship between the sequence, structure, binding energy, binding kinetics and binding thermodynamics of protein-protein interactions is crucial to understanding cellular signaling, the assembly and regulation of molecular complexes, the mechanisms through which mutations lead to disease, and protein engineering. Results: We present SKEMPI 2.0, a major update to our database of binding free energy changes upon mutation for structurally resolved protein-protein interactions. This version now contains manually curated binding data for 7085 mutations, an increase of 133%, including changes in kinetics for 1844 mutations, enthalpy and entropy changes for 443 mutations, and 440 mutations, which abolish detectable binding. Availability and implementation: The database is available as supplementary data and at https://life.bsc.es/pid/skempi2/. Supplementary information: Supplementary data are available at Bioinformatics online.

Summary: The PPI3D web server is focused on searching and analyzing the structural data on protein-protein interactions. Reducing the data redundancy by clustering and analyzing the properties of interaction interfaces using Voronoi tessellation makes this software a highly effective tool for addressing different questions related to protein interactions. Availability and Implementation: The server is freely accessible at http://bioinformatics.lt/software/ppi3d/ . Contact: [email protected]. Supplementary information: Supplementary data are available at Bioinformatics online.