A5001029093- Enzyme Structure and Function
- Protein Structure and Dynamics
- RNA and protein synthesis mechanisms
- Computational Drug Discovery Methods
- Tuberculosis Research and Epidemiology
- Biochemical and Molecular Research
- DNA Repair Mechanisms
- Mycobacterium research and diagnosis
- Glycosylation and Glycoproteins Research
- Enzyme Production and Characterization
- Genomics and Phylogenetic Studies
- Monoclonal and Polyclonal Antibodies Research
- Fibroblast Growth Factor Research
- CRISPR and Genetic Engineering
- Bioinformatics and Genomic Networks
- Biochemical and Structural Characterization
- Microtubule and mitosis dynamics
- Microbial Natural Products and Biosynthesis
- Machine Learning in Bioinformatics
- Neurological diseases and metabolism
- Mass Spectrometry Techniques and Applications
- Protein Kinase Regulation and GTPase Signaling
- Peptidase Inhibition and Analysis
- DNA and Nucleic Acid Chemistry
- Porphyrin Metabolism and Disorders
University of Cambridge
2015-2024
European Bioinformatics Institute
2012-2021
Universidad de Zaragoza
2020-2021
University of Oxford
1969-2019
Cambridge Crystallographic Data Centre
2019
University of Modena and Reggio Emilia
2016
The Gurdon Institute
2016
Indian Institute of Technology Madras
2015
Czech Academy of Sciences, Biology Centre
2011-2013
St Vincents Institute of Medical Research
2013
Drug development has a high attrition rate, with poor pharmacokinetic and safety properties significant hurdle. Computational approaches may help minimize these risks. We have developed novel approach (pkCSM) which uses graph-based signatures to develop predictive models of central ADMET for drug development. pkCSM performs as well or better than current methods. A freely accessible web server (http://structure.bioc.cam.ac.uk/pkcsm), retains no information submitted it, provides an...
Abstract Motivation: Mutations play fundamental roles in evolution by introducing diversity into genomes. Missense mutations structural genes may become either selectively advantageous or disadvantageous to the organism affecting protein stability and/or interfering with interactions between partners. Thus, ability predict impact of on and is significant value, particularly understanding effects Mendelian somatic progression disease. Here, we propose a novel approach study missense...
The TRANSPARENT TESTA GLABRA1 (TTG1) locus regulates several developmental and biochemical pathways in Arabidopsis, including the formation of hairs on leaves, stems, roots, production seed mucilage anthocyanin pigments. TTG1 has been isolated by positional cloning, its identity was confirmed complementation a ttg1 mutant. encodes protein 341 amino acid residues with four WD40 repeats. is similar to AN11, regulator biosynthesis petunia, more distantly related those β subunits heterotrimeric...
The sheer volume of non-synonymous single nucleotide polymorphisms that have been generated in recent years from projects such as the Human Genome Project, HapMap Project and Genome-Wide Association Studies means it is not possible to characterize all mutations experimentally on gene products, i.e. elucidate effects protein structure function.However, automatic methods can predict will allow a reduced set be studied.Site Directed Mutator (SDM) statistical potential energy function uses...
Abstract We describe a database of protein structure alignments for homologous families. The HOMSTRAD presently contains 130 families and 590 aligned structures, which have been selected on the basis quality X‐ray analysis accuracy structure. For each family, provides structure‐based alignment derived using COMPARER annotated with JOY in special format that represents local structural environment amino acid residue. also set superposed atomic coordinates obtained MNYFIT, can be viewed...
Here, we report a webserver for the improved SDM, used predicting effects of mutations on protein stability. As pioneering knowledge-based approach, SDM has been highlighted as most appropriate method to use in combination with many other approaches. We have updated environment-specific amino-acid substitution tables based current expanded PDB (a 5-fold increase information), and introduced new residue-conformation interaction parameters, including packing density residue depth. The server...
Interactions between proteins and their ligands, such as small molecules, other proteins, DNA, depend on specific interatomic interactions that can be classified the basis of atom type distance angle constraints. Visualisation these provides insights into nature molecular recognition events has practical uses in guiding drug design understanding structural functional impacts mutations. We present Arpeggio, a web server for calculating within protein, or small-molecule including van der...
An approach is described for modelling the three-dimensional structure of a protein from tertiary structures several homologous proteins that have been determined by X-ray analysis. A method developed simultaneous superposition molecules and calculation an ‘average structure’ or ‘framework’. Investigation convergence properties this method, in case both weighted unweighted least squares, demonstrates give unique answer latter robust family proteins. Multi-dimensional scaling used to subgroup...
Succinate dehydrogenase B (SDHB) and D (SDHD) subunit gene mutations predispose to adrenal extraadrenal pheochromocytomas, head neck paragangliomas (HNPGL), other tumor types. We report risks in 358 patients with SDHB (n=295) SDHD (n=63) mutations. Risks of HNPGL pheochromocytoma mutation carriers were 29% 52%, respectively, at age 60 years 71% 29%, carriers. malignant renal tumors (14% 70 years) higher carriers; 55 different (including a novel recurrent exon 1 deletion) identified. No clear...
Abstract The accurate scoring of rigid‐body docking orientations represents one the major difficulties in protein–protein prediction. Other challenges are development faster and more efficient sampling methods introduction receptor ligand flexibility during simulations. Overall, good discrimination near‐native poses from very early stages protein is essential step before applying costly interface refinement to correct solutions. Here we explore a simple approach poses, which has been...