BACKGROUND: Statistical potentials, also named knowledge-based potentials, are scoring functions derived from empirical data that can be used to evaluate the quality of protein folds and protein-protein interaction (PPI) structures. In previous works we decomposed the statistical potentials in different terms, named Split-Statistical Potentials, accounting for the type of amino acid pairs, their hydrophobicity, solvent accessibility and type of secondary structure. These potentials have been successfully used to identify near-native structures in protein structure prediction, rank protein docking poses, and predict PPI binding affinities. RESULTS: Here, we present the SPServer, a web server that applies the Split-Statistical Potentials to analyze protein folds and protein interfaces. SPServer provides global scores as well as residue/residue-pair profiles presented as score plots and maps. This level of detail allows users to: (1) identify potentially problematic regions on protein structures; (2) identify disrupting amino acid pairs in protein interfaces; and (3) compare and analyze the quality of tertiary and quaternary structural models. CONCLUSIONS: While there are many web servers that provide scoring functions to assess the quality of either protein folds or PPI structures, SPServer integrates both aspects in a unique easy-to-use web server. Moreover, the server permits to locally assess the quality of the structures and interfaces at a residue level and provides tools to compare the local assessment between structures. SERVER ADDRESS: https://sbi.upf.edu/spserver/ .

Motivation: The characterization of the protein-protein association mechanisms is crucial to understanding how biological processes occur. It has been previously shown that the early formation of non-specific encounters enhances the realization of the stereospecific (i.e. native) complex by reducing the dimensionality of the search process. The association rate for the formation of such complex plays a crucial role in the cell biology and depends on how the partners diffuse to be close to each other. Predicting the binding free energy of proteins provides new opportunities to modulate and control protein-protein interactions. However, existing methods require the 3D structure of the complex to predict its affinity, severely limiting their application to interactions with known structures. Results: We present a new approach that relies on the unbound protein structures and protein docking to predict protein-protein binding affinities. Through the study of the docking space (i.e. decoys), the method predicts the binding affinity of the query proteins when the actual structure of the complex itself is unknown. We tested our approach on a set of globular and soluble proteins of the newest affinity benchmark, obtaining accuracy values comparable to other state-of-art methods: a 0.4 correlation coefficient between the experimental and predicted values of ΔG and an error < 3 Kcal/mol. Availability and implementation: The binding affinity predictor is implemented and available at http://sbi.upf.edu/BADock and https://github.com/badocksbi/BADock. Contact: [email protected] or [email protected]. Supplementary information: Supplementary data are available at Bioinformatics online.