A5025471816- Protein Structure and Dynamics
- RNA and protein synthesis mechanisms
- Enzyme Structure and Function
- Machine Learning in Bioinformatics
- Genomics and Phylogenetic Studies
- Microbial Metabolic Engineering and Bioproduction
- Advanced Proteomics Techniques and Applications
- Computational Drug Discovery Methods
- Mass Spectrometry Techniques and Applications
- Microbial Natural Products and Biosynthesis
- Glycosylation and Glycoproteins Research
- Influenza Virus Research Studies
- Bacteriophages and microbial interactions
- Bioinformatics and Genomic Networks
- Biochemical and Molecular Research
- RNA modifications and cancer
- Vibrio bacteria research studies
- Cancer Genomics and Diagnostics
- Patient Safety and Medication Errors
- Pharmaceutical Practices and Patient Outcomes
- Hemoglobin structure and function
- Salmonella and Campylobacter epidemiology
- Photosynthetic Processes and Mechanisms
- Aquaculture disease management and microbiota
- Machine Learning in Materials Science
The University of Texas Southwestern Medical Center
2015-2025
Southwestern Medical Center
2021-2023
Howard Hughes Medical Institute
2014-2018
University of Washington
2008-2011
Deep learning takes on protein folding In 1972, Anfinsen won a Nobel prize for demonstrating connection between protein’s amino acid sequence and its three-dimensional structure. Since 1994, scientists have competed in the biannual Critical Assessment of Structure Prediction (CASP) protein-folding challenge. methods took center stage at CASP14, with DeepMind’s Alphafold2 achieving remarkable accuracy. Baek et al . explored network architectures based DeepMind framework. They used three-track...
Understanding the evolution of a protein, including both close and distant relationships, often reveals insight into its structure function. Fast easy access to such up-to-date information facilitates research. We have developed hierarchical evolutionary classification all proteins with experimentally determined spatial structures, presented it as an interactive updatable online database. ECOD (Evolutionary Classification protein Domains) is distinct from other structural classifications in...
Recent advances in protein structure prediction have generated accurate structures of previously uncharacterized human proteins. Identifying domains these predicted and classifying them into an evolutionary hierarchy can reveal biological insights. Here, we describe the detection classification from proteome. Our indicates that only 62% residues are located globular domains. We further classify observe majority (65%) be classified among known folds by sequence, with a smaller fraction (33%)...
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 biological insights. Using our Evolutionary Classification Domains (ECOD) from experimental structures as a basis for classification, we describe detection and cataloging domains 48 whole proteomes deposited AlphaFold Database. On average, provide positive classification (either or other identifiable non-domain...
Abstract The Pfam protein families database is a comprehensive collection of domains and used for genome annotation structure function analysis (https://www.ebi.ac.uk/interpro/). This update describes major developments in since 2020, including decommissioning the website integration with InterPro, harmonization ECOD structural classification, expanded curation metagenomic, microprotein repeat-containing families. We highlight how AlphaFold predictions are being leveraged to refine domain...
Evolutionary Classification Of protein Domains (ECOD) (http://prodata.swmed.edu/ecod) comprehensively classifies with known spatial structures maintained by the Protein Data Bank (PDB) into evolutionary groups of domains. ECOD relies on a combination automatic and manual weekly updates to achieve its high accuracy coverage short update cycle. approximately 120 000 depositions PDB more than 500 domains in ∼3400 homologous groups. We show performance pipeline since release ECOD, describe...
ABSTRACT ECOD (Evolutionary Classification Of protein Domains) is a comprehensive and up‐to‐date structure classification database. The majority of new structures released from the PDB (Protein Data Bank) each week already have close homologs in hierarchy thus can be reliably partitioned into domains classified by software without manual intervention. However, those proteins that lack confidently detectable require careful analysis experts. Although many bioinformatics resources rely on...
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 function can be complicated. We define a minimal Rossmann-like structure motif (RLM) that corresponds the common core known use this to identify all RLM Protein Data Bank (PDB), thus finding constitute about 20% 3D structures. The Evolutionary Classification protein...
This report describes the tertiary structure prediction assessment of difficult modeling targets in 14th round Critical Assessment Structure Prediction (CASP14). We implemented an official ranking scheme that used same scores as previous CASP topology-based assessment, but combined these with one emphasized physically realistic models. The top performing AlphaFold2 group outperformed rest community on all two considered this assessment. They provided high quality models for most (86% over...
The recent breakthroughs in structure prediction, where methods such as AlphaFold demonstrated near-atomic accuracy, herald a paradigm shift structural biology. 200 million high-accuracy models released the Database are expected to guide protein science coming decades. Partitioning these into domains and assigning them an evolutionary hierarchy provide efficient way gain functional insights proteins. However, classifying large number of predicted structures challenges infrastructure current...
Abstract The evolutionary classification of protein domains (ECOD) classifies using a combination sequence and structural data (http://prodata.swmed.edu/ecod). Here we present the culmination our previous efforts at classifying from predicted structures, principally AlphaFold Database (AFDB), by integrating these with existing PDB structures. This combined includes both previous, purely experimental, as well provisional 48 proteomes in AFDB model organisms concern to global health. ECOD over...
An evolutionary-based definition and classification of target evaluation units (EUs) is presented for the 14th round critical assessment structure prediction (CASP14). CASP14 targets included 84 experimental models submitted by various structural groups (designated T1024-T1101). Targets were split into EUs based on domain organization available templates performance server groups. Several required splitting (19 out 25 multidomain targets) due in part to observed conformation changes. All...
Abstract DeepMind presented remarkably accurate protein structure predictions at the CASP14 conference. We explored network architectures incorporating related ideas and obtained best performance with a 3-track in which information 1D sequence level, 2D distance map 3D coordinate level is successively transformed integrated. The produces accuracies approaching those of CASP14, enables rapid solution challenging X-ray crystallography cryo-EM modeling problems, provides insights into functions...
The goal of Dynameomics is to perform atomistic molecular dynamics (MD) simulations representative proteins from all known folds in explicit water their native state and along thermal unfolding pathways. Here we present 188-fold representatives analyses. These 188 targets represent 67% the structures Protein Data Bank. behavior several specific highlighted illustrate general properties full dataset demonstrate role MD understanding protein function stability. As an example what can be...
Salmonella enterica is a pathogenic bacterium known for causing severe typhoid fever in humans, making it important to study due its potential health risks and significant impact on public health. This provides evolutionary classification of proteins from pangenome. We classified 17,238 domains 13,147 79,758 strains studied detail 272 14 characterized pathogenicity islands (SPIs). Among SPIs-related proteins, 90 function the secretion machinery. 41% SPI have no previous sequence annotation....
Post-translational modifications (PTMs) play a crucial role in allowing cells to expand the functionality of their proteins and adaptively regulate signaling pathways. Defects PTMs have been linked numerous developmental disorders human diseases, including cancer, diabetes, heart, neurodegenerative metabolic diseases. are important targets drug discovery, as they can significantly influence various aspects interactions binding affinity. The structural consequences PTMs, such...
Abstract Domain classification of protein predictions released in the AlphaFold Database (AFDB) has been a recent focus Evolutionary Classification Domains (ECOD). Although primary our work partition and assignment domains from these predictions, we here show how diverse can be used to examine reference domain set more closely. Using results DPAM, AlphaFold‐specific parsing algorithm, hierarchical groupings that share significant levels homologous links, both between groups were not...
ABSTRACT Protein target structures for the Critical Assessment of Structure Prediction round 11 (CASP11) and CASP ROLL were split into domains classified categories suitable assessment template‐based modeling (TBM) free (FM) based on their evolutionary relatedness to existing by Evolutionary Classification Domains (ECOD) database. First, divided domain‐based evaluation units. Target splits domain organization available templates as well performance servers whole targets compared domains....
Abstract Interactions between proteins and small organic compounds play a crucial role in regulating protein functions. These interactions can modulate various aspects of behavior, including enzymatic activity, signaling cascades, structural stability. By binding to specific sites on proteins, induce conformational changes, alter protein–protein interactions, or directly affect catalytic activity. Therefore, many drugs available the market today are molecules (72% all approved last 5 years)....