ECOD: integrating classifications of protein domains from experimental and predicted structures.

The evolutionary classification of protein domains (ECOD) classifies protein domains using a combination of sequence and structural data (http://prodata.swmed.edu/ecod).

DrugDomain: The evolutionary context of drugs and small molecules bound to domains.

Interactions between proteins and small organic compounds play a crucial role in regulating protein functions. These interactions can modulate various aspects of protein behavior, including enzymatic activity, signaling cascades, and structural stability. By binding to specific sites on proteins, small organic compounds can induce conformational changes, alter protein-protein interactions, or directly affect catalytic activity.

Structure classification of the proteins from Salmonella enterica pangenome revealed novel potential pathogenicity islands.

Salmonella enterica is a pathogenic bacterium known for causing severe typhoid fever in humans, making it important to study due to its potential health risks and significant impact on public health. This study provides evolutionary classification of proteins from Salmonella enterica pangenome. We classified 17,238 domains from 13,147 proteins from 79,758 Salmonella enterica strains and studied in detail domains of 272 proteins from 14 characterized Salmonella pathogenicity islands (SPIs).

ECOD domain classification of 48 whole proteomes from AlphaFold Structure Database using DPAM2.

Protein structure prediction has now been deployed widely across several different large protein sets. Large-scale domain annotation of these predictions can aid in the development of biological insights. Using our Evolutionary Classification of Protein Domains (ECOD) from experimental structures as a basis for classification, we describe the detection and cataloging of domains from 48 whole proteomes deposited in the AlphaFold Database.

Deep Learning for Subtypes Identification of Pure Seminoma of the Testis.

The most critical step in the clinical diagnosis workflow is the pathological evaluation of each tumor sample. Deep learning is a powerful approach that is widely used to enhance diagnostic accuracy and streamline the diagnosis process. In our previous study using omics data, we identified 2 distinct subtypes of pure seminoma.

Pathogenic mutation hotspots in protein kinase domain structure.

Control of eukaryotic cellular function is heavily reliant on the phosphorylation of proteins at specific amino acid residues, such as serine, threonine, tyrosine, and histidine. Protein kinases that are responsible for this process comprise one of the largest families of evolutionarily related proteins. Dysregulation of protein kinase signaling pathways is a frequent cause of a large variety of human diseases including cancer, autoimmune, neurodegenerative, and cardiovascular disorders.

Pan-cancer structurome reveals overrepresentation of beta sandwiches and underrepresentation of alpha helical domains.

The recent progress in the prediction of protein structures marked a historical milestone. AlphaFold predicted 200 million protein models with an accuracy comparable to experimental methods. Protein structures are widely used to understand evolution and to identify potential drug targets for the treatment of various diseases, including cancer.

Seminoma subtypes differ in the organization and functional state of the immune microenvironment.

Unlabelled: Seminoma is the most common type of testicular germ cell tumors (TGCTs) among 15-44 years old men. Seminoma treatments include orchiectomy, platinum-based chemotherapy and radiotherapy. These radical treatment methods cause up to 40 severe adverse long-term side effects including secondary cancers.

Integrated Molecular Analysis Reveals 2 Distinct Subtypes of Pure Seminoma of the Testis.

Objective: Testicular germ cell tumors (TGCT) are the most common solid malignancy in adolescent and young men, with a rising incidence over the past 20 years. Overall, TGCTs are second in terms of the average life years lost per person dying of cancer, and clinical therapeutics without adverse long-term side effects are lacking. Platinum-based regimens for TGCTs have heterogeneous outcomes even within the same histotype that frequently leads to under- and over-treatment.

DisEnrich: database of enriched regions in human dark proteome.

Motivation: Intrinsically disordered proteins (IDPs) are involved in numerous processes crucial for living organisms. Bias in amino acid composition of these proteins determines their unique biophysical and functional features. Distinct intrinsically disordered regions (IDRs) with compositional bias play different important roles in various biological processes.

Completeness and Consistency in Structural Domain Classifications.

Domain classifications are a useful resource for computational analysis of the protein structure, but elements of their composition are often opaque to potential users. We perform a comparative analysis of our classification ECOD against the SCOPe, SCOP2, and CATH domain classifications with respect to their constituent domain boundaries and hierarchal organization. The coverage of these domain classifications with respect to ECOD and to the PDB was assessed by structure and by sequence.

A Fifth of the Protein World: Rossmann-like Proteins as an Evolutionarily Successful Structural unit.

The Rossmann-like fold is the most prevalent and diversified doubly-wound superfold of ancient evolutionary origin. Rossmann-like domains are present in a variety of metabolic enzymes and are capable of binding diverse ligands. Discerning evolutionary relationships among these domains is challenging because of their diverse functions and ancient origin.

Recent advances suggest increased influence of selective pressure in allostery.

Allosteric regulation of protein functions is ubiquitous in organismal biology, but the principles governing its evolution are not well understood. Here we discuss recent studies supporting the large-scale existence of latent allostery in ancestor proteins of superfamilies. As suggested, the evolution of allostery could be driven by the need for specificity in paralogs of slow evolving protein complexes with conserved active sites.

Functional analysis of Rossmann-like domains reveals convergent evolution of topology and reaction pathways.

Rossmann folds are ancient, frequently diverged domains found in many biological reaction pathways where they have adapted for different functions. Consequently, discernment and classification of their homologous relations and function can be complicated. We define a minimal Rossmann-like structure motif (RLM) that corresponds for the common core of known Rossmann domains and use this motif to identify all RLM domains in the Protein Data Bank (PDB), thus finding they constitute about 20% of all known 3D structures.

ECOD: identification of distant homology among multidomain and transmembrane domain proteins.

The manual classification of protein domains is approaching its 20th anniversary. ECOD is our mixed manual-automatic domain classification. Over time, the types of proteins which require manual curation has changed.

Functional and evolutionary analysis of viral proteins containing a Rossmann-like fold.

Viruses are the most abundant life form and infect practically all organisms. Consequently, these obligate parasites are a major cause of human suffering and economic loss. Rossmann-like fold is the most populated fold among α/β-folds in the Protein Data Bank and proteins containing Rossmann-like fold constitute 22% of all known proteins 3D structures.

High temperature and pressure influence the interdomain orientation of Nip7 proteins from P. abyssi and P. furiosus: MD simulations.

Interactions between protein domains and their position and movement relative to each other are essential for the stability and normal functioning of a protein molecule. Features of the movement of domains may define the mechanism of enzymatic reactions. Therefore, the description of this motion is an important task in the analysis of the structures and functions of multidomain proteins.

Identification of residues of the archaeal RNA-binding Nip7 proteins specific to environmental conditions.

The understanding of biological and molecular mechanisms providing survival of cells under extreme temperatures and pressures will help to answer fundamental questions related to the origin of life and to design of biotechnologically important enzymes with new properties. Here, we analyze amino acid sequences of the Nip7 proteins from 35 archaeal species to identify positions containing mutations specific to the hydrostatic pressure and temperature of organism's habitat. The number of such positions related to pressure change is much lower than related to temperature change.

Molecular dynamics simulations of the Nip7 proteins from the marine deep- and shallow-water Pyrococcus species.

Background: The identification of the mechanisms of adaptation of protein structures to extreme environmental conditions is a challenging task of structural biology. We performed molecular dynamics (MD) simulations of the Nip7 protein involved in RNA processing from the shallow-water (P. furiosus) and the deep-water (P.