A5086160124- Enzyme Structure and Function
- Protein Structure and Dynamics
- Advanced Electron Microscopy Techniques and Applications
- RNA and protein synthesis mechanisms
- Genomics and Phylogenetic Studies
- Microtubule and mitosis dynamics
- Electron and X-Ray Spectroscopy Techniques
- Cellular transport and secretion
- RNA modifications and cancer
- Machine Learning in Bioinformatics
- Phytochemicals and Medicinal Plants
- Glycosylation and Glycoproteins Research
- Machine Learning in Healthcare
- Machine Learning in Materials Science
- Bacteriophages and microbial interactions
- Force Microscopy Techniques and Applications
- Genomics and Chromatin Dynamics
- Vascular Malformations Diagnosis and Treatment
- Viral Infections and Immunology Research
- Genetics and Neurodevelopmental Disorders
- Genomics and Rare Diseases
- Medical Imaging Techniques and Applications
- Topic Modeling
- Scientific Computing and Data Management
- HIV/AIDS drug development and treatment
Science and Technology Facilities Council
2014-2024
Research Complex at Harwell
2017-2024
Georgia State University
2024
Rutherford Appleton Laboratory
2014-2023
Australia and New Zealand Banking Group
2023
Birkbeck, University of London
2016-2021
Institute of Structural and Molecular Biology
2016-2021
University College London
2017-2020
Inserm
2009-2019
University of London
2019
Sporadic vascular malformations (VMs) are complex congenital anomalies of blood vessels that lead to stroke, life-threatening bleeds, disfigurement, overgrowth, and/or pain. Therapeutic options severely limited, and multidisciplinary management remains challenging, particularly for high-flow arteriovenous (AVM).To investigate the pathogenesis sporadic intracranial extracranial VMs in 160 children which known genetic causes had been excluded, we sequenced DNA from affected tissue optimized...
Abstract This paper describes outcomes of the 2019 Cryo-EM Model Challenge. The goals were to (1) assess quality models that can be produced from cryogenic electron microscopy (cryo-EM) maps using current modeling software, (2) evaluate reproducibility results different software developers and users (3) compare performance metrics used for model evaluation, particularly Fit-to-Map metrics, with focus on near-atomic resolution. Our findings demonstrate relatively high accuracy cryo-EM derived...
The TCP transcription factors control multiple developmental traits in diverse plant species. Members of this family share an approximately 60-residue-long domain that binds to DNA. is predicted form a basic helix-loop-helix (bHLH) structure but shares little sequence similarity with canonical bHLH domain. This classifies the as novel class DNA binding specific kingdom. Little known about how interacts its target We report biochemical characterization and properties member Arabidopsis...
As the resolutions of Three Dimensional Electron Microscopic reconstructions biological macromolecules are being improved, there is a need for better fitting and refinement methods at high robust approaches model assessment. Flex-EM/MODELLER has been used flexible atomic models in intermediate-to-low resolution density maps different systems. Here, we demonstrate suitability method to successfully refine structures higher (2.5-4.5Å) using both simulated experimental data, including newly...
Krishna Tulsi, a member of Lamiaceae family, is herb well known for its spiritual, religious and medicinal importance in India. The common name this plant 'Tulsi' (or 'Tulasi' or 'Thulasi') considered sacred by Hindus. We present the draft genome Ocimum tenuiflurum L (subtype Tulsi) report. paired-end mate-pair sequence libraries were generated whole sequenced with Illumina Hiseq 1000, resulting an assembled 374 Mb, coverage 61 % (612 Mb estimated size). have also studied transcriptomes...
Abstract The membrane attack complex (MAC) is one of the immune system’s first responders. Complement proteins assemble on target membranes to form pores that lyse pathogens and impact tissue homeostasis self-cells. How MAC disrupts barrier remains unclear. Here we use electron cryo-microscopy flicker spectroscopy show interacts with lipid bilayers in two distinct ways. Whereas C6 C7 associate outer leaflet reduce energy for bending, C8 C9 traverse bilayer increasing rigidity. CryoEM...
With the immense growth in number of available protein structures, fast and accurate structure comparison has been essential. We propose an efficient method for comparison, based on a structural alphabet. Protein Blocks (PBs) is widely used alphabet with 16 pentapeptide conformations that can fairly approximate complete chain. Thus 3D be translated into 1D sequence PBs. simple Needleman–Wunsch approach raw PB substitution matrix, PB-based alignments were better than many popular methods....
Background Secondary structures are elements of great importance in structural biology, biochemistry and bioinformatics. They broadly composed two repetitive namely α-helices β-sheets, apart from turns, the rest is associated to coil. These secondary have specific conserved biophysical geometric properties. PolyProline II (PPII) helix yet another interesting structure which less frequent not usually with stabilizing interactions. Recent studies shown that PPII frequency higher than expected,...
Three-dimensional electron microscopy is currently one of the most promising techniques used to study macromolecular assemblies. Rigid and flexible fitting atomic models into density maps often essential gain further insights assemblies they represent. Currently, tools that facilitate assessment fitted are needed. TEMPy (template comparison using Python) a toolkit designed for this purpose. The library includes set methods assess fits in intermediate-to-low resolution maps, both globally...
Abstract Background Childhood‐onset dystonia is often genetically determined. Recently, KMT2B variants have been recognized as an important cause of childhood‐onset dystonia. Objective To define the frequency mutations in a cohort dystonic patients aged <18 years at onset, associated clinical and radiological phenotype, natural history disease. Methods Whole‐exome sequencing or customized gene panels were used to screen 65 who had previously tested negative for all other known...
Recent developments in 3-dimensional electron microcopy (3D-EM) techniques and a concomitant drive to look at complex molecular structures, have led rapid increase the amount of volume data available for biomolecules. This creates demand better methods analyse data, including improved scores comparison, classification integration different resolutions. To this end, we developed evaluated set scoring functions that compare 3D-EM volumes. test our used benchmark alignments derived from...
We present TopoStats, a Python toolkit for automated editing and analysis of Atomic Force Microscopy images. The program automates identification tracing individual molecules in circular linear conformations without user input. TopoStats was able to identify trace range within AFM images, finding, on average, ~90% all molecular assemblies wide field view, the need prior processing. DNA minicircles varying size, origami rings pore forming proteins were identified accurately traced with...
Kinesin motors play diverse roles in mitosis and are targets for antimitotic drugs. The clinical significance of these emphasizes the importance understanding molecular basis their function. Equally important, investigations into modes inhibition provide crucial information about mechanisms. Kif18A regulates spindle microtubules through its dual functionality, with microtubule-based stepping regulation microtubule dynamics. We investigated mechanism by small molecule BTB-1. motor domain...
Aerial biomass and its associated physicochemical properties are pivotal components in understanding ecosystem dynamics, with far-reaching implications for environmental agricultural management. This study delves into the dynamics of aerial correlation properties, utilizing a dataset derived from research on Spartina alterniflora Cape Fear Estuary North Carolina. Machine learning (ML) models, including Response Surface Methodology (RSM), Quadratic Model, Artificial Neural Networks (ANN),...
MKLP2, a kinesin-6, has critical roles during the metaphase-anaphase transition and cytokinesis. Its motor domain contains conserved nucleotide binding motifs, but is divergent in sequence (~35% identity) size (~40% larger) compared to other kinesins. Using cryo-electron microscopy biophysical assays, we have undertaken mechanochemical dissection of microtubule-bound MKLP2 its ATPase cycle, show that many facets mechanism are distinct from While neck-linker directed towards microtubule...
Structural determination of molecular complexes by cryo-EM requires large, often complex processing the image data that are initially obtained. Here, TEMPy 2, an update package to process, optimize and assess maps structures fitted them, is described. New optimization routines, comprehensive automated checks workflows perform these tasks
Cryogenic electron microscopy (cryo-EM) is a powerful technique for determining structures of multiple conformational or compositional states macromolecular assemblies involved in cellular processes. Recent technological developments have led to leap the resolution many cryo-EM data sets, making atomic model building more common interpretation. We present method calculating differences between two maps map and fitted model. The proposed approach works by scaling using amplitude matching...
Abstract Structures of macromolecular assemblies derived from cryo-EM maps often contain errors that become more abundant with decreasing resolution. Despite efforts in the community to develop metrics for map and atomistic model validation, thus far, no specific scoring have been applied systematically assess interface between assembly subunits. Here, we comprehensively assessed protein–protein interfaces by cryo-EM. To this end, developed Protein Interface-score (PI-score), a...