No abstract

No abstract

Protein Blocks (PBs) are a widely used structural alphabet describing local protein backbone conformation in terms of 16 possible conformational states, adopted by five consecutive amino acids. The representation of complex protein 3D structures as 1D PB sequences was previously successfully applied to protein structure alignment and protein structure prediction. In the current study, we present a new model, PYTHIA (predicting any conformation at high accuracy), for the prediction of the protein local conformations in terms of PBs directly from the amino acid sequence. PYTHIA is based on a deep residual inception-inside-inception neural network with convolutional block attention modules, predicting 1 of 16 PB classes from evolutionary information combined to physicochemical properties of individual amino acids. PYTHIA clearly outperforms the LOCUSTRA reference method for all PB classes and demonstrates great performance for PB prediction on particularly challenging proteins from the CASP14 free modelling category.

Understanding the functions and origins of proteins requires splitting these macromolecules into fragments that could be independent in terms of folding, activity, or evolution. For that purpose, structural domains are the typical level of analysis, but shorter segments, such as subdomains and supersecondary structures, are insightful as well. Here, we propose SWORD2, a web server for exploring how an input protein structure may be decomposed into ‘Protein Units’ that can be hierarchically assembled to delimit structural domains. For each partitioning solution, the relevance of the identified substructures is estimated through different measures. This multilevel analysis is achieved by integrating our previous work on domain delineation, ‘protein peeling’ and model quality assessment. We hope that SWORD2 will be useful to biologists searching for key regions in their proteins of interest and to bioinformaticians building datasets of protein structures. The web server is freely available online: https://www.dsimb.inserm.fr/SWORD2.

Motivation Alignment of protein structures is a major problem in structural biology. The first approach commonly used is to consider proteins as rigid bodies. However, alignment of protein structures can be very complex due to conformational variability, or complex evolutionary relationships between proteins such as insertions, circular permutations or repetitions. In such cases, introducing flexibility becomes useful for two reasons: (i) it can help compare two protein chains which adopted two different conformational states, such as due to proteins/ligands interaction or post-translational modifications, and (ii) it aids in the identification of conserved regions in proteins that may have distant evolutionary relationships. Results We propose ICARUS, a new approach for flexible structural alignment based on identification of Protein Units, evolutionarily preserved structural descriptors of intermediate size, between secondary structures and domains. ICARUS significantly outperforms reference methods on a dataset of very difficult structural alignments. Availability and implementation code is freely available online at https://github.com/DSIMB/ICARUS. Supplementary information Supplementary data are available at Bioinformatics online.