A5031545090- Protein Structure and Dynamics
- Enzyme Structure and Function
- RNA and protein synthesis mechanisms
- Genomics and Phylogenetic Studies
- Biochemical and Structural Characterization
- RNA Research and Splicing
- Bacterial Genetics and Biotechnology
- RNA modifications and cancer
- Bacterial biofilms and quorum sensing
- Computational Drug Discovery Methods
- Bacteriophages and microbial interactions
- Machine Learning in Bioinformatics
- Advanced Electron Microscopy Techniques and Applications
- Bioinformatics and Genomic Networks
- Microbial Metabolic Engineering and Bioproduction
- Connective Tissue Growth Factor Research
- Glycosylation and Glycoproteins Research
- Mass Spectrometry Techniques and Applications
- Streptococcal Infections and Treatments
- Genetic Associations and Epidemiology
- Biofuel production and bioconversion
- Genomics and Rare Diseases
- Microbial Natural Products and Biosynthesis
- Antimicrobial Peptides and Activities
- Peptidase Inhibition and Analysis
Age UK
2024
Genomics (United Kingdom)
2024
European Bioinformatics Institute
2018-2023
Paul Scherrer Institute
2017-2021
ETH Zurich
2017-2019
A correct assessment of the quaternary structure proteins is a fundamental prerequisite to understanding their function, physico-chemical properties and mode interaction with other proteins. Currently about 90% structures in Protein Data Bank are crystal structures, which embedded lattice among number contacts. Computational methods required 1) classify all protein-protein contacts lattices as biologically relevant or 2) provide an how interfaces combine into biological assembly. In our...
Abstract We present the results of first independent assessment protein assemblies in CASP. A total 1624 oligomeric models were submitted by 108 predictor groups for 30 targets CASP12 edition. evaluated accuracy predictions comparison to their reference structures at interface patch and residue contact levels. find that patches are more reliably predicted than specific contacts. Whereas none 15 hard have successful contacts interface, six with resemblance patch. Successful exist all suitable...
Abstract Genome sequencing efforts have led to the discovery of tens millions protein missense variants found in human population with majority these having no annotated role and some likely contributing trait variation disease. Sequence-based artificial intelligence approaches become highly accurate at predicting that are detrimental function proteins but they do not inform on mechanisms disruption. Here we combined sequence structure-based methods perform proteome-wide prediction...
BioJava is an open-source project that provides a Java library for processing biological data. The aims to simplify bioinformatic analyses by implementing parsers, data structures, and algorithms common tasks in genomics, structural biology, ontologies, phylogenetics, more. Since 2012, we have released two major versions of the (4 5) include many new features tackle challenges with increasingly complex macromolecular structure requires 8 or higher freely available under LGPL 2.1 license....
Abstract RNA polymerase I (Pol I) specifically synthesizes ribosomal RNA. Pol upregulation is linked to cancer, while mutations in the machinery lead developmental disorders. Here we report cryo-EM structure of elongating human at 2.7 Å resolution. In exit tunnel, observe a double-stranded helix that may support processivity. Our confirms consists 13 subunits with only one subunit forming stalk. Additionally, complex initiation factor RRN3 3.1 resolution reveals stalk flipping upon binding....
We present the assembly category assessment in 13th edition of CASP community-wide experiment. For second time, protein assemblies constitute an independent category. Compared to last we see a clear uptake participation, more oligomeric targets released, and consistent, albeit modest, improvement predictions quality. Looking at tertiary structure predictions, observe that ignoring state hinders modeling success. also note some contact prediction groups successfully predicted homomeric...
Many proteins fold into highly regular and repetitive three dimensional structures. The analysis of structural patterns repeated elements is fundamental to understand protein function evolution. We present recent improvements the CE-Symm tool for systematically detecting analyzing internal symmetry repeats in proteins. In addition accurate detection symmetry, now capable i) reporting type ii) identifying smallest repeating unit, iii) describing arrangement with transformation operations...
Significance The structure of single and tandem SHIRT domains from the streptococcal surface protein Sgo_0707 were determined. In conjunction with biophysics molecular dynamics simulations, results show that observed gene length variation would result in differential projection host ligand binding domain on bacterial cell surface. An analysis long-read DNA sequence data reveals many other repetitive proteins appear to undergo variation. We propose these variable-length “Periscope Proteins”...
groups A and B cause serious infections, including early onset sepsis meningitis in newborns. Rib domain-containing surface proteins are found associated with invasive strains elicit protective immunity animal models. Yet, despite their apparent importance infection, the structure of domain was previously unknown. Structures single domains differing length reveal a rare case atrophy through deletion 2 core antiparallel strands, resulting loss an entire sheet β-sandwich from...
Abstract Background Fibrillar adhesins are long multidomain proteins that form filamentous structures at the cell surface of bacteria. They an important yet understudied class composed adhesive and stalk domains mediate interactions bacteria with their environment. This study aims to characterize fibrillar in a wide range bacterial phyla identify new adhesin-like improve our understanding host-bacteria interactions. Results Through careful literature computational searches, we identified 82...
Abstract Our goal is to answer the question: compared with experimental structures, how useful are predicted models for functional annotation? We assessed utility of by comparing performances a suite methods characterization on predictions and structures. identified 28 sites in 25 protein targets perform assessment. These included nine known ligand binding (holo‐sites), that expected or suggested authors small molecule (apo‐sites), Ten containing important motifs, loops, key residues...
Protein Language Models (PLMs) have emerged as performant and scalable tools for predicting the functional impact clinical significance of protein-coding variants, but they still lag experimental accuracy. Here, we present a novel fine-tuning approach to improve performance PLMs with maps variant effects from Deep Mutational Scanning (DMS) assays using Normalised Log-odds Ratio (NLR) head. We find consistent improvements in held-out protein test set, on independent DMS annotation benchmarks...
Abstract Summary Proteins with highly similar tandem domains have shown an increased propensity for misfolding and aggregation. Several molecular explanations been put forward, such as swapping of adjacent domains, but there is a lack computational tools to systematically analyze them. We present the TAndem DOmain Swap Stability predictor (TADOSS), method computationally estimate stability domain-swapped conformations from structures single based on previous coarse-grained simulation...
The members of the CCN (Cyr61/CTGF/Nov) family are a group matricellular regulatory proteins that essential to wide range functional pathways in cell signalling. Through interacting with extracellular matrix components and growth factors via one their four domains, involved critical biological processes such as angiogenesis, proliferation, bone development, fibrogenesis tumorigenesis. Here, crystal structure thrombospondin module 1 (TSP1) domain CCN3 (previously known Nov) is presented,...
Abstract Bacterial fibrillar adhesins are specialized extracellular polypeptides that promote the attachment of bacteria to surfaces other cells or materials. Adhesin‐mediated interactions critical for establishment and persistence stable bacterial populations within diverse environmental niches important determinants virulence. The fibronectin (Fn)‐binding adhesin CshA, its paralogue CshB, play roles in host colonization by oral commensal opportunistic pathogen Streptococcus gordonii . As...
Abstract Many proteins fold into highly regular and repetitive three dimensional structures. The analysis of structural patterns repeated elements is fundamental to understand protein function evolution. We present recent improvements the CE-Symm tool for systematically detecting analyzing internal symmetry repeats in proteins. In addition accurate detection symmetry, now capable i) reporting type ii) identifying smallest repeating unit, iii) describing arrangement with transformation...
Abstract RNA polymerase I (Pol I) specifically synthesizes ribosomal RNA. Pol upregulation is linked to cancer, while mutations in the machinery lead developmental disorders. Here, we report cryo-EM structure of elongating human at 2.7 Å resolution. In exit tunnel, observe a double-stranded helix that may support processivity. Our confirms consists 13 subunits with only one subunit forming stalk. Additionally, complex initiation factor RRN3 3.1 resolution reveals stalk flipping upon binding....
Abstract A correct assessment of the quaternary structure proteins is a fundamental prerequisite to understanding their function, physico-chemical properties and mode interaction with other proteins. Currently about 90% structures in Protein Data Bank are crystal structures, which embedded lattice among number contacts. Computational methods required 1) classify all protein-protein contacts lattices as biologically relevant or 2) provide an how interfaces combine into biological assembly In...
ABSTRACT RNA polymerase III (Pol III) synthesises tRNAs and other short, essential RNAs. Human Pol misregulation is linked to tumour transformation, neurodegenerative developmental disorders, increased sensitivity viral infections. inhibition increases longevity in different animals but also promotes intracellular bacterial growth owing its role the immune system. This highlights importance better understand human transcription on a molecular level. Here, we present cryo-EM structures at 2.8...
<ns4:p>Proteins undergo large structural rearrangements such as circular permutations, dimerisation via domain swapping, and loss of core secondary structure elements in atrophy, among others. These changes can be naturally represented distance matrix transformations, exploiting their conserved native residue contacts at the protein core. Here we present an homology modelling approach to formulate a Euclidean (EDM) problem use it build 3D structures. This aims lightweight, flexible fast,...