BackgroundProtein-protein interactions are crucial for normal biological processes and to regulate cellular reactions that affect gene expression and function. Several previous studies have emphasized the roles of residues at the interface of protein-protein complexes in conferring stability and specificity to the complex. Interface residues in a protein are well known for their interactions with sidechain and main chain atoms with the interacting protein. However, the extent of intra-protein interactions involving interface residues in a protein-protein complex and their relative contribution in comparison to inter-protein interactions are not clearly understood. This paper probes this feature using a dataset of protein-protein complexes of known 3-D structure.ResultsWe have analysed a dataset of 45 transient protein-protein complex structures with at least one of the interacting proteins with a known structure available also in the unbound form. We observe that a large proportion of interface residues (1608 out of 2137 interface residues, 75%) are involved in intra and inter-protein interactions simultaneously. The amino acid propensities of such interfacial residues involved in bifurcated interactions are found to be highly similar to the general propensities to occur at protein-protein interfaces. Finally, we observe that a majority (83%) of intra-protein interactions of interface residues with bifurcated interactions, are also observed in the protein uncomplexed form.ConclusionsWe have shown, to the best of our knowledge for the first time, that a vast majority of the protein-protein interface residues are involved in extensive intra-protein interactions apart from inter-protein interactions. For a majority of such interface residues the microenvironment in the tertiary structure is pre-formed and retained upon complex formation with its cognate partner during transient interactions.ReviewersThis article was reviewed by Arumay Pal and Mallur Madhusudhan.Electronic supplementary materialThe online version of this article (10.1186/s13062-019-0232-2) contains supplementary material, which is available to authorized users.

Background: RNA-binding proteins (RBPs) have been extensively studied in humans over the past few years. Multiple reports have been made in the literature for genome-wide survey for this class of proteins in the human genome using different tools and techniques. Due to the inherent difference in the nature of the methods used in identifying human RBPs, as well as the diverse sources for data collection in each of these studies, there exists immense heterogeneity (including diversity in data formats) and poor intersection among the datasets available from the different studies.Description: hRBPome is a comprehensive database of human RBPs known from six different studies. We have introduced considerable uniformity in the data, by mapping the various data formats reported by the different studies to gene names. This makes comparison across studies (datasets) easier than was possible before. We also provide confidence scores to each of these known RBPs, on the basis of their presence across studies. Conclusion:This database presents a set of 837 high confidence RBP genes, identified in three or more resources, out of the six studies considered. Hence, it forms a "gold standard"for RBPs in the human genome. It also provides information for all the human RBPs from multiple resources, known to the best of our knowledge, on a common platform. The database can be accessed from the following URL: http://caps.ncbs.res.in/hrbpome Keywords database / RNA-binding proteins / human / genes / comparison

Disulphide bonds are stabilizing crosslinks in proteins and serve to enhance their thermal stability. In proteins that are small and rich in disulphide bonds, they could be the major determining factor for the choice of conformational state since their constraints on appropriate backbone conformation can be substantial. Such crosslinks and their positional conservation could itself enable protein family and functional association. Despite the importance of the field, there is no comprehensive database on disulphide crosslinks that is available to the public. Herein we provide information on disulphides in DSDBASE2.0, an updated and significantly expanded database that is freely available, fully annotated and manually curated database on native and modelled disulphides. The web interface also provides several useful computational tools that have been specifically developed for proteins containing disulphide crosslinks. The modelling of disulphide crosslinks is performed using stereochemical criteria, coded within our Modelling of Disulphides in Proteins (MODIP) algorithm. The inclusion of modelled disulphides potentially enhances the loop database substantially, thereby permitting the recognition of compatible polypeptide segments that could serve as templates for immediate modelling. The DSDBASE2.0 database has been updated to include 153,944 PDB entries, 216,096 native and 20,153,850 modelled disulphide bond segments from PDB January 2021 release. The current database also provides a resource to user-friendly search for multiple disulphide bond containing loops, along with annotation of their function using GO and subcellular localization of the query. Furthermore, it is possible to obtain the three-dimensional models of disulphide-rich small proteins using an independent algorithm, RANMOD, that generates and examines random, but allowed backbone conformations of the polypeptide. DSDBASE2.0 still remains the largest open-access repository that organizes all disulphide bonds of proteins on a single platform. The database can be accessed from http://caps.ncbs.res.in/dsdbase2.

Since proteins evolve by divergent evolution, proteins with distant homology to each other may or may not bear similar functions. Improved computational approaches are required to recognize distant homologues that are functionally similar. One of the methods of assigning function to sequences is to use profiles derived from sequences of known structure. We describe an update of the Genomic Distribution of protein structural domain Superfamilies (GenDiS) database, namely GenDiS+, which provides a projection of SCOP superfamily members on the sequence space (NR database, NCBI). The sequences are validated using structure-based sequence alignment profiles and domain and full-length sequence alignments. GenDiS+ is a `tour de force’ for detecting homologues within around 160 000 taxonomic identifiers, starting from nearly 11 000 domains of known structure. Features, like full-sequence alignment and phylogeny, domain sequence alignment and phylogeny, list of associated structural and sequence domains with strength of interactions, links to databases like Pfam, UniProt and ModBase and list of sequences with a PDB structure, are provided.