All Outputs (31)

Long-range correlations in the mechanics of small DNA circles under topological stress revealed by multi-scale simulation (2016)
Journal Article
Sutthibutpong, T., Matek, M., Benham, C., Slade, G. G., Noy, A., Laughton, C. A., …Harris, S. A. (2016). Long-range correlations in the mechanics of small DNA circles under topological stress revealed by multi-scale simulation. Nucleic Acids Research, 44(19), 9121–9130. https://doi.org/10.1093/nar/gkw815

It is well established that gene regulation can be achieved through activator and repressor proteins that bind to DNA and switch particular genes on or off, and that complex metabolic networks deter- mine the levels of transcription of a given gene a... Read More about Long-range correlations in the mechanics of small DNA circles under topological stress revealed by multi-scale simulation.

The fitness burden imposed by synthesising quorum sensing signals (2016)
Journal Article
Ruparell, A., Dubern, J., Ortori, C. A., Harrison, F., Halliday, N., Emtage, A., …Hardie, K. R. (2016). The fitness burden imposed by synthesising quorum sensing signals. Scientific Reports, 6, Article 33101. https://doi.org/10.1038/srep33101

It is now well established that bacterial populations utilize cell-to-cell signaling (quorum-sensing, QS) to control the production of public goods and other co-operative behaviours. Evolutionary theory predicts that both the cost of signal productio... Read More about The fitness burden imposed by synthesising quorum sensing signals.

GPCRs through the keyhole: the role of protein flexibility in ligand binding to ?-adrenoceptors (2016)
Journal Article
Emtage, A. L., Mistry, S. N., Fischer, P. M., Kellam, B., & Laughton, C. A. (2017). GPCRs through the keyhole: the role of protein flexibility in ligand binding to ?-adrenoceptors. Journal of Biomolecular Structure and Dynamics, 35(12), 2604-2619. https://doi.org/10.1080/07391102.2016.1226197

© 2016 Informa UK Limited, trading as Taylor & Francis Group. G protein-coupled receptors (GPCRs) are proteins of pharmaceutical importance, with over 30% of all drugs in clinical use targeting them. Increasing numbers of X-ray crystal (XRC) struct... Read More about GPCRs through the keyhole: the role of protein flexibility in ligand binding to ?-adrenoceptors.

Parmbsc1: a refined force field for DNA simulations (2015)
Journal Article
Ivani, I., Dans, P. D., Noy, A., Pérez, A., Faustino, I., Hospital, A., …Orozco, M. (2016). Parmbsc1: a refined force field for DNA simulations. Nature Methods, 13(1), 55-61. https://doi.org/10.1038/NMETH.3658

We present parmbsc1, a force field for DNA atomistic simulation, which has been parameterized from high-level quantum mechanical data and tested for nearly 100 systems (representing a total simulation time of ?140 ?s) covering most of DNA structural... Read More about Parmbsc1: a refined force field for DNA simulations.

Multiscale modelling of drug-polymer nanoparticle assembly identifies parameters influencing drug encapsulation efficiency (2015)
Journal Article
Mackenzie, R., Booth, J., Alexander, C., Garnett, M., & Laughton, C. A. (2015). Multiscale modelling of drug-polymer nanoparticle assembly identifies parameters influencing drug encapsulation efficiency. Journal of Chemical Theory and Computation, 11(6), https://doi.org/10.1021/ct501152a

Using a multiscale (dual resolution) approach combining an atomistic (GROMOS96) and coarse-grain (MARTINI) force field, we have been able to simulate the process of drug-polymer nanoparticle assembly by nanoprecipitation from mixed solvents. Here we... Read More about Multiscale modelling of drug-polymer nanoparticle assembly identifies parameters influencing drug encapsulation efficiency.

In vitro antitumor mechanism of (E)-N-(2-methoxy-5-(((2,4,6-trimethoxystyryl)sulfonyl)methyl)pyridin-3-yl)methanesulfonamide (2014)
Journal Article
Lu, T., Laughton, C., Wang, S., & Bradshaw, T. (2015). In vitro antitumor mechanism of (E)-N-(2-methoxy-5-(((2,4,6-trimethoxystyryl)sulfonyl)methyl)pyridin-3-yl)methanesulfonamide. Molecular Pharmacology, 87(1), 18-30. doi:10.1124/mol.114.093245

ON01910.Na [sodium (E)-2-(2-methoxy-5-((2,4,6-trimethoxystyrylsulfonyl)methyl)phenylamino)acetate; Rigosertib, Estybon], a styryl benzylsulfone, is a phase III stage anticancer agent. This non-ATP competitive kinase inhibitor has multitargeted activi... Read More about In vitro antitumor mechanism of (E)-N-(2-methoxy-5-(((2,4,6-trimethoxystyryl)sulfonyl)methyl)pyridin-3-yl)methanesulfonamide.

Investigation of the flexibility of protein kinases implicated in the pathology of Alzheimer's Disease (2014)
Journal Article
Laughton, C., Mazanetz, M., & Fischer, P. (2014). Investigation of the flexibility of protein kinases implicated in the pathology of Alzheimer's Disease. Molecules, 19(7), 9134-9159. https://doi.org/10.3390/molecules19079134

The pathological characteristics of Alzheimer’s Disease (AD) have been linked to the activity of three particular kinases—Glycogen Synthase Kinase 3β (GSK3β), Cyclin-Dependent Kinase 5 (CDK5) and Extracellular-signal Regulated Kinase 2 (ERK2). As a c... Read More about Investigation of the flexibility of protein kinases implicated in the pathology of Alzheimer's Disease.

Investigating the binding preferences of small molecule inhibitors of human protein arginine methyltransferase 1 using molecular modelling (2014)
Journal Article
Hong, W., Laughton, C. A., Li, J., Yap, L. F., Paterson, I. C., & Wang, H. (2014). Investigating the binding preferences of small molecule inhibitors of human protein arginine methyltransferase 1 using molecular modelling. Journal of Molecular Graphics and Modelling, 51, 193-202. https://doi.org/10.1016/j.jmgm.2014.05.010

Protein arginine methyltransferases (PRMTs) catalyse the methylation of arginine residues of target proteins. PRMTs utilise S-adenosyl methionine (SAM) as the methyl group donor, leading to S-adenosyl homocysteine (SAH) and monomethylarginine (mMA).... Read More about Investigating the binding preferences of small molecule inhibitors of human protein arginine methyltransferase 1 using molecular modelling.

Conversion of a non-selective adenosine receptor antagonist into A 3-selective high affinity fluorescent probes using peptide-based linkers (2013)
Journal Article
Vernall, A. J., Stoddart, L. A., Briddon, S. J., Ng, H. W., Laughton, C. A., Doughty, S. W., …Kellam, B. (2013). Conversion of a non-selective adenosine receptor antagonist into A 3-selective high affinity fluorescent probes using peptide-based linkers. Organic and Biomolecular Chemistry, 11(34), 5673-5682. https://doi.org/10.1039/c3ob41221k

Advances in fluorescence-based imaging technologies have helped propel the study of real-time biological readouts and analysis across many different areas. In particular the use of fluorescent ligands as chemical tools to study proteins such as G pro... Read More about Conversion of a non-selective adenosine receptor antagonist into A 3-selective high affinity fluorescent probes using peptide-based linkers.

Functional interplay of DnaE polymerase, DnaG primase and DnaC helicase within a ternary complex, and primase to polymerase hand-off during lagging strand DNA replication in Bacillus subtilis (2013)
Journal Article
Rannou, O., Le Chatelier, E., Larson, M. A., Nouri, H., Dalmais, B., Laughton, C., …Soultanas, P. (2013). Functional interplay of DnaE polymerase, DnaG primase and DnaC helicase within a ternary complex, and primase to polymerase hand-off during lagging strand DNA replication in Bacillus subtilis. Nucleic Acids Research, 41(10), https://doi.org/10.1093/nar/gkt207

Bacillus subtilis has two replicative DNA polymerases. PolC is a processive high-fidelity replicative polymerase, while the error-prone DnaEBs extends RNA primers before hand-off to PolC at the lagging strand. We show that DnaEBs interacts with t... Read More about Functional interplay of DnaE polymerase, DnaG primase and DnaC helicase within a ternary complex, and primase to polymerase hand-off during lagging strand DNA replication in Bacillus subtilis.

The effects of a telomere destabilising agent on cancer cell-cycle dynamics - integrated modelling and experiments (2012)
Journal Article
Hirt, B. V., Wattis, J. A., Preston, S. P., & Laughton, C. A. (2012). The effects of a telomere destabilising agent on cancer cell-cycle dynamics - integrated modelling and experiments. Journal of Theoretical Biology, 295, https://doi.org/10.1016/j.jtbi.2011.10.038

The pentacyclic acridinium salt RHPS4 displays anti-tumour properties in vitro as well as in vivo and is potentially cell-cycle specific. We have collected experimental data and formulated a compartmental model using ordinary differential equations t... Read More about The effects of a telomere destabilising agent on cancer cell-cycle dynamics - integrated modelling and experiments.