A5078919568- Computational Drug Discovery Methods
- Microbial Metabolic Engineering and Bioproduction
- Protein Structure and Dynamics
- Enzyme Catalysis and Immobilization
- Pharmacogenetics and Drug Metabolism
- Enzyme Structure and Function
- Metabolomics and Mass Spectrometry Studies
- Analytical Chemistry and Chromatography
- Advanced Proteomics Techniques and Applications
- Chemical Synthesis and Analysis
- Protein purification and stability
- Biofuel production and bioconversion
- Machine Learning and Algorithms
- Biochemical and Molecular Research
- Spectroscopy and Chemometric Analyses
- Endoplasmic Reticulum Stress and Disease
- Bioinformatics and Genomic Networks
- Plant biochemistry and biosynthesis
- Pesticide and Herbicide Environmental Studies
- Mathematical Approximation and Integration
- RNA and protein synthesis mechanisms
- Environmental Toxicology and Ecotoxicology
- Microbial Natural Products and Biosynthesis
- Peptidase Inhibition and Analysis
- Algorithms and Data Compression
European Bioinformatics Institute
2017-2024
Wellcome Trust
2017-2024
Optibrium (United Kingdom)
2016
University of Cambridge
2012-2014
Unilever (United Kingdom)
2012-2014
M-CSA (Mechanism and Catalytic Site Atlas) is a database of enzyme active sites reaction mechanisms that can be accessed at www.ebi.ac.uk/thornton-srv/m-csa. Our objectives with are to provide an open data resource for the community browse known catalytic sites, use dataset understand function evolution. results from merging two existing databases, MACiE (Mechanism, Annotation Classification in Enzymes), mechanisms, CSA (Catalytic Atlas), enzymes. We releasing as new website underlying...
Abstract The Protein Data Bank in Europe-Knowledge Base (PDBe-KB, https://pdbe-kb.org) is a community-driven, collaborative resource for literature-derived, manually curated and computationally predicted structural functional annotations of macromolecular structure data, contained the (PDB). goal PDBe-KB two-fold: (i) to increase visibility reduce fragmentation contributed by specialist data resources, make these more findable, accessible, interoperable reusable (FAIR) (ii) place their...
FAst MEtabolizer (FAME) is a fast and accurate predictor of sites metabolism (SoMs). It based on collection random forest models trained diverse chemical data sets more than 20 000 molecules annotated with their experimentally determined SoMs. Using comprehensive set available data, FAME aims to assess metabolic processes from holistic point view. not limited specific enzyme family or species. Besides global model, dedicated are for human, rat, dog metabolism; prediction phase I II also...
Metabolism of xenobiotic and endogenous compounds is frequently complex, not completely elucidated, therefore often ambiguous. The prediction sites metabolism (SoM) can be particularly helpful as a first step toward the identification metabolites, process especially relevant to drug discovery. This paper describes reactivity approach for predicting SoM whereby derived directly from ground state ligand molecular orbital analysis, calculated using Density Functional Theory, novel...
We describe methods for predicting cytochrome P450 (CYP) metabolism incorporating both pathway-specific reactivity and isoform-specific accessibility considerations. Semiempirical quantum mechanical (QM) simulations, parametrized using experimental data ab initio calculations, estimate the of each potential site (SOM) in context whole molecule. Ligand-based models, trained high-quality regioselectivity data, correct orientation steric effects different CYP isoform binding pockets. The...
Over the years, hundreds of enzyme reaction mechanisms have been studied using experimental and simulation methods. This rich literature on biological catalysis is now ripe for use as foundation new knowledge-based approaches to investigate mechanisms. Here, we present a tool able automatically infer mechanistic paths given three-dimensional active site reaction, based set catalytic rules compiled from Mechanism Catalytic Site Atlas, database EzMechanism (pronounced 'Easy' Mechanism)...
There are numerous applications that use the structures of protein-ligand complexes from PDB, such as 3D pharmacophore identification, virtual screening, and fragment-based drug design. The underlying these potentially much more informative if they contain biologically relevant bound ligands, with high similarity to cognate ligands. We present a study ligand-enzyme compares enabling best matches be identified. calculate molecular scores using method called PARITY (proportion atoms residing...
Abstract Motivation Cofactors are essential for many enzyme reactions. The Protein Data Bank (PDB) contains >67 000 entries containing structures, with bound cofactor or cofactor-like molecules. This work aims to identify and categorize these small molecules in the PDB make it easier find them. Results Europe (PDBe; pdbe.org) has implemented a pipeline molecules, which now part of PDBe weekly release process. Availability implementation Information is made available on individual...
Abstract Background The prediction of sites and products metabolism in xenobiotic compounds is key to the development new chemical entities, where screening potential metabolites for toxicity or unwanted side-effects crucial importance. In this work 2D topological fingerprints are used encode atomic three probabilistic machine learning methods applied: Parzen-Rosenblatt Window (PRW), Naive Bayesian (NB) a novel approach called RASCAL (Random Attribute Subsampling Classification ALgorithm)....
The discovery of protein-ligand-binding sites is a major step for elucidating protein function and investigating new functional roles. Detecting experimentally time-consuming expensive. Thus, variety in silico methods to detect predict binding was proposed as they can be scalable, fast present low cost.We Graph-based Residue neighborhood Strategy Predict (GRaSP), novel residue centric scalable method ligand-binding site residues. It based on supervised learning strategy that models the...
Abstract Proteins are essential macromolecules for the maintenance of living systems. Many them perform their function by interacting with other molecules in regions called binding sites. The identification and characterization these fundamental importance to determine protein function, being a step processes such as drug design discovery. However, identifying is not trivial due drawbacks experimental methods, which costly time-consuming. Here we propose GRaSP-web, web server that uses GRaSP...
Transform-MinER (Transforming Molecules in Enzyme Reactions) is a web application facilitating the exploration of chemical biosynthetic space, guiding user toward promising start points for enzyme design projects or directed evolution experiments. Two types search are possible: Molecule Search allows to submit source substrate enabling reactions acting on similar substrates, whereas Path additionally target molecule path substrates link and target. searches potential reaction centers uses...
One goal of synthetic biology is to make new enzymes generate products, but identifying the starting for further investigation often elusive and relies on expert knowledge, intensive literature searching trial error.We present Transform Molecules in Enzyme Reactions, an online computational tool that transforms query substrate molecules into products using enzyme reactions. The most similar native reactions each transformation are found, highlighting those may be interest design directed...
Tunnels in enzymes with buried active sites are key structural features allowing the entry of substrates and release products, thus contributing to catalytic efficiency. Targeting bottlenecks protein tunnels is also a powerful engineering strategy. However, identification functional multiple structures non-trivial task that can only be addressed computationally. We present pipeline integrating automated analysis an in-house machine-learning predictor for annotation pockets, followed by...
Most molecules are transformed and transported by specific metabolising enzymes transporters resulting in changes their bioactivities, pharmacokinetics toxicity profiles. This is a key consideration the design of drugs. Ideally, when medicines have performed task, they need to fade away gracefully, not introduce unexpected or untoward biological effects. Some examples predictive metabolism, transport interesting considerations drugs described.