A5088004559- Cancer Genomics and Diagnostics
- Genomics and Phylogenetic Studies
- Lung Cancer Treatments and Mutations
- SARS-CoV-2 and COVID-19 Research
- RNA modifications and cancer
- Fibroblast Growth Factor Research
- Bioinformatics and Genomic Networks
- Epigenetics and DNA Methylation
- Animal Virus Infections Studies
- Influenza Virus Research Studies
- Machine Learning in Bioinformatics
- interferon and immune responses
- Protein Structure and Dynamics
- Systemic Lupus Erythematosus Research
- Atherosclerosis and Cardiovascular Diseases
- Immune Cell Function and Interaction
- Kruppel-like factors research
- Radiomics and Machine Learning in Medical Imaging
- Cancer-related molecular mechanisms research
- Enzyme Structure and Function
- COVID-19 Clinical Research Studies
- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- Ferroptosis and cancer prognosis
- Eosinophilic Disorders and Syndromes
Institute of Structural and Molecular Biology
2016-2025
University College London
2016-2025
London Cancer
2022
Royal London Hospital
2021
Birkbeck, University of London
2012-2016
Abstract CATH (https://www.cathdb.info) identifies domains in protein structures from wwPDB and classifies these into evolutionary superfamilies, thereby providing structural functional annotations. There are two levels: CATH-B, a daily snapshot of the latest domain superfamily assignments, CATH+, with additional derived data, such as predicted sequence domains, functionally coherent subsets (Functional Families or FunFams). The CATH+ release, version 4.3, significantly increases coverage an...
The latest version of the CATH-Gene3D protein structure classification database (4.0, http://www.cathdb.info) provides annotations for over 235 000 domain structures and includes 25 million predictions.This article an update on major developments in 2 years since last publication this journal including: significant improvements to predictive power our functional families (FunFams); release 'current' putative assignments (CATH-B); a new, strictly non-redundant data set CATH domains suitable...
The latest version of the CATH-Gene3D protein structure classification database has recently been released (version 4.1, http://www.cathdb.info). resource comprises over 300 000 domain structures and 53 million domains classified into 2737 homologous superfamilies, doubling number predicted in previous version. daily-updated CATH-B, which contains our very assignment data, provides putative classifications for 100 additional domains. This article describes developments to last two years...
Abstract In this study, the impact of apolipoprotein B mRNA-editing catalytic subunit-like (APOBEC) enzyme APOBEC3B (A3B) on epidermal growth factor receptor (EGFR)-driven lung cancer was assessed. A3B expression in EGFR mutant (EGFRmut) non-small-cell (NSCLC) mouse models constrained tumorigenesis, while tumors treated with EGFR-targeted therapy associated treatment resistance. Analyses human NSCLC showed upregulation and revealed therapy-induced activation nuclear kappa (NF-κB) as an...
This article provides an update of the latest data and developments within CATH protein structure classification database (http://www.cathdb.info). The resource two levels release: CATH-B, a daily snapshot structural domain boundaries superfamily assignments, CATH+, which adds layers derived data, such as predicted sequence domains, functional annotations clustering (known Functional Families or FunFams). most recent CATH+ release (version 4.2) huge in coverage data. increases number fully-...
Abstract SARS-CoV-2 has a zoonotic origin and was transmitted to humans via an undetermined intermediate host, leading infections in other mammals. To enter host cells, the viral spike protein (S-protein) binds its receptor, ACE2, is then processed by TMPRSS2. Whilst receptor binding contributes range, S-protein:ACE2 complexes from animals have not been investigated widely. predict infection risks, we modelled 215 vertebrate species, calculated changes energy of complex caused mutations each...
// Harshnira Patani 1, * , Tom D. Bunney Nethaji Thiyagarajan 1 Richard A. Norman 2 Derek Ogg Jason Breed Paul Ashford Andrew Potterton Mina Edwards Sarah V. Williams 3 Gary S. Thomson 4 Camilla S.M. Pang Margaret Knowles Alexander L. Breeze Christine Orengo Chris Phillips Matilda Katan Institute of Structural and Molecular Biology, Division Biosciences, University College London, Gower St, London WC1E 6BT, UK Discovery Sciences, AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire...
Fibroblast growth factor receptors (FGFRs) are recognized therapeutic targets in cancer. We here describe insights underpinning the impact of mutations on FGFR1 and FGFR3 kinase activity drug efficacy, using a combination computational calculations experimental approaches including cellular studies, X-ray crystallography biophysical biochemical measurements. Our findings reveal that some tested compounds, particular TKI258, could provide opportunity not only for patients with primary...
Gene3D http://gene3d.biochem.ucl.ac.uk is a database of domain annotations Ensembl and UniProtKB protein sequences. Domains are predicted using library profile HMMs representing 2737 CATH superfamilies. has previously featured in the Database issue NAR here we report updates to website database. The current (v14) release expanded its assignments ∼20 000 cellular genomes over 43 million unique sequences, more than doubling number sequences since our last publication. Amongst other updates,...
The search for druggable pockets on the surface of a protein is often performed single conformer, treated as rigid body. Transient may be missed in this approach. Here, we describe methodology systematic silico analysis clefts across multiple conformers metastable α1-antitrypsin (A1AT). Pathological mutations disturb conformational landscape A1AT, triggering polymerisation that leads to emphysema and hepatic cirrhosis. Computational screens small molecule inhibitors have generally focused...
Abstract Tumour sequencing identifies highly recurrent point mutations in cancer driver genes, but rare functional are hard to distinguish from large numbers of passengers. We developed a novel computational platform applying multi-modal approach filter out passengers and more robustly identify putative genes. The primary enrichment CATH families (CATH-FunFams) – structurally functionally coherent sets evolutionary related domains. Using structural representatives CATH-FunFams, we...
Abstract SARS-CoV-2 has a zoonotic origin and was transmitted to humans via an undetermined intermediate host, leading infections in other mammals. To enter host cells, the viral spike protein (S-protein) binds its receptor, ACE2, is then processed by TMPRSS2. Whilst receptor binding contributes range, S-protein:ACE2 complexes from animals have not been investigated widely. predict infection risks, we modelled 215 vertebrate species, calculated changes energy of complex caused mutations each...
Human herpesviruses are widespread human pathogens with a remarkable impact on worldwide public health. Despite intense decades of research, the molecular details in many aspects their function remain to be fully characterized. To unravel how these viruses operate, thorough understanding relationships between involved components is key. Here, we present HVint, novel protein-protein intraviral interaction resource for herpes simplex virus type 1 (HSV-1) integrating data from five external...
Abstract The COVID-19 disease is an ongoing global health concern. Although vaccination provides some protection, people are still susceptible to re-infection. Ostensibly, certain populations or clinical groups may be more vulnerable. Factors causing these differences unclear and whilst socioeconomic cultural likely important, human genetic factors could influence susceptibility. Experimental studies indicate SARS-CoV-2 uses innate immune suppression as a strategy speed-up entry replication...
// Benedetta Lombardi 1, 2, * , Paul Ashford Aurelio A. Moya-Garcia 2 Aleksander Rust Mark Crawford 1 Sarah V. Williams 3 Margaret Knowles Matilda Katan Christine Orengo and Jasminka Godovac-Zimmermann Proteomics Molecular Cell Dynamics, Center for Nephrology, School of Life Medical Sciences, University College London, London NW3 2PF, United Kingdom Institute Structural Biology, Division Biosciences, WC1E 6BT, Section Oncology, Leeds Medicine, St James's Hospital, LS9 7TF, Joint first...
Coronavirus-like organisms have been previously identified in Arthropod ectoparasites (such as ticks and unfed cat flea). Yet, the question regarding possible role of these arthropods SARS-CoV-2 passive/biological transmission vectors is still poorly explored. In this study, we performed silico structural binding energy calculations to assess risks associated with ectoparasite transmission. We found sufficient similarity between ACE human ACE2 protein sequences build good quality 3D-models...
Abstract Background Protein structures provide a valuable resource for rational drug design. For protein with no known ligand, computational tools can predict surface pockets that are of suitable size and shape to accommodate complementary small-molecule drug. However, pocket prediction against single static may miss features arise from proteins' dynamic behaviour. In particular, ligand-binding conformations be observed as transiently populated states the apo protein, so it is possible gain...
Abstract Women with Systemic Lupus Erythematosus (SLE) show significantly increased cardiovascular risk compared to the general population. However, despite CVD being a major cause of morbidity and mortality for these women, this is not managed clinically tools dissect predict their are lacking. Notably, elevated captured by traditional factors. To explore molecular programs underlying asymptomatic atherosclerosis in SLE we used well-characterised cohort CVD-free women SLE, scanned...
Abstract The COVID-19 disease is an ongoing global health concern. Although vaccination provides some protection, people are still susceptible to re-infection. Ostensibly, certain populations or clinical groups may be more vulnerable. Factors causing these differences unclear and whilst socioeconomic cultural likely important, human genetic factors could influence susceptibility. Experimental studies indicate SARS-CoV-2 uses innate immune suppression as a strategy speed-up entry replication...
Tumour sequencing identifies highly recurrent point mutations in cancer driver genes, but rare functional are hard to distinguish from large numbers of passengers. We developed a novel computational platform applying multi-modal approach filter out passengers and more robustly identify putative genes. The primary enrichment CATH families (CATH-FunFams) – structurally functionally coherent sets evolutionary related domains. Using structural representatives CATH-FunFams, we subsequently seek...