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All Outputs (24)

Optimizing Excipient Properties to Prevent Aggregation in Biopharmaceutical Formulations (2023)
Journal Article
King, T. E., Humphrey, J. R., Laughton, C. A., Thomas, N. R., & Hirst, J. D. (2024). Optimizing Excipient Properties to Prevent Aggregation in Biopharmaceutical Formulations. Journal of Chemical Information and Modeling, 64(1), 265–275. https://doi.org/10.1021/acs.jcim.3c01898

Excipients are included within protein biotherapeutic solution formulations to improve colloidal and conformational stability but are generally not designed for the specific purpose of preventing aggregation and improving cryoprotection in solution.... Read More about Optimizing Excipient Properties to Prevent Aggregation in Biopharmaceutical Formulations.

Design, Synthesis, and Application of Fluorescent Ligands Targeting the Intracellular Allosteric Binding Site of the CXC Chemokine Receptor 2 (2023)
Journal Article
Casella, B. M., Farmer, J. P., Nesheva, D. N., Williams, H. E., Charlton, S. J., Holliday, N. D., …Mistry, S. N. (2023). Design, Synthesis, and Application of Fluorescent Ligands Targeting the Intracellular Allosteric Binding Site of the CXC Chemokine Receptor 2. Journal of Medicinal Chemistry, https://doi.org/10.1021/acs.jmedchem.3c00849

The inhibition of CXC chemokine receptor 2 (CXCR2), a key inflammatory mediator, is a potential strategy in the treatment of several pulmonary diseases and cancers. The complexity of endogenous chemokine interaction with the orthosteric binding site... Read More about Design, Synthesis, and Application of Fluorescent Ligands Targeting the Intracellular Allosteric Binding Site of the CXC Chemokine Receptor 2.

Linear Binary Classifier to Predict Bacterial Biofilm Formation on Polyacrylates (2023)
Journal Article
Contreas, L., Hook, A. L., Winkler, D. A., Figueredo, G., Williams, P., Laughton, C. A., …Williams, P. M. (2023). Linear Binary Classifier to Predict Bacterial Biofilm Formation on Polyacrylates. ACS Applied Materials and Interfaces, 15(11), 14155-14163. https://doi.org/10.1021/acsami.2c23182

Bacterial infections are increasingly problematic due to the rise of antimicrobial resistance. Consequently, the rational design of materials naturally resistant to biofilm formation is an important strategy for preventing medical device-associated i... Read More about Linear Binary Classifier to Predict Bacterial Biofilm Formation on Polyacrylates.

In Vitro Anticancer Properties of Novel Bis-Triazoles (2022)
Journal Article
Saleh, M. M., Abuarqoub, D. A., Hammad, A. M., Hossan, M. S., Ahmed, N., Aslam, N., …Bradshaw, T. D. (2023). In Vitro Anticancer Properties of Novel Bis-Triazoles. Current Issues in Molecular Biology, 45(1), 175-196. https://doi.org/10.3390/cimb45010014

Here, we describe the anticancer activity of our novel bis-triazoles MS47 and MS49, developed previously as G-quadruplex stabilizers, focusing specifically upon the human melanoma MDA-MB-435 cell line. At the National Cancer Institute (NCI), USA, bis... Read More about In Vitro Anticancer Properties of Novel Bis-Triazoles.

Development of fluorescent peptide G protein-coupled receptor activation biosensors for NanoBRET characterization of intracellular allosteric modulators (2022)
Journal Article
Farmer, J. P., Mistry, S. N., Laughton, C. A., & Holliday, N. D. (2022). Development of fluorescent peptide G protein-coupled receptor activation biosensors for NanoBRET characterization of intracellular allosteric modulators. FASEB Journal, 36(11), Article e22576. https://doi.org/10.1096/fj.202201024R

G protein-coupled receptors (GPCRs) are widely therapeutically targeted, and recent advances in allosteric modulator development at these receptors offer further potential for exploitation. Intracellular allosteric modulators (IAM) represent a class... Read More about Development of fluorescent peptide G protein-coupled receptor activation biosensors for NanoBRET characterization of intracellular allosteric modulators.

GLIMPS: A Machine Learning Approach to Resolution Transformation for Multiscale Modeling (2021)
Journal Article
Louison, K. A., Louison, K. A., Dryden, I. L., & Laughton, C. A. (2021). GLIMPS: A Machine Learning Approach to Resolution Transformation for Multiscale Modeling. Journal of Chemical Theory and Computation, 17(12), 7930-7937. https://doi.org/10.1021/acs.jctc.1c00735

We describe a general approach to transforming molecular models between different levels of resolution, based on machine learning methods. The approach uses a matched set of models at both levels of resolution for training, but requires only the coor... Read More about GLIMPS: A Machine Learning Approach to Resolution Transformation for Multiscale Modeling.

Ligand-induced conformational selection predicts the selectivity of cysteine protease inhibitors (2019)
Journal Article
Sartori, G. R., Leitão, A., Montanari, C. A., & Laughton, C. A. (2019). Ligand-induced conformational selection predicts the selectivity of cysteine protease inhibitors. PLoS ONE, 14(12), Article e0222055. https://doi.org/10.1371/journal.pone.0222055

Cruzain, a cysteine protease of Trypanosoma cruzi, is a validated target for the treatment of Chagas disease. Due to its high similarity in three-dimensional structure with human cathepsins and their sequence identity above 70% in the active site reg... Read More about Ligand-induced conformational selection predicts the selectivity of cysteine protease inhibitors.

Principal nested shape space analysis of molecular dynamics data (2019)
Journal Article
Dryden, I. L., Kim, K., Laughton, C. A., & Le, H. (2019). Principal nested shape space analysis of molecular dynamics data. Annals of Applied Statistics, 13(4), 2213-2234. https://doi.org/10.1214/19-AOAS1277

Molecular dynamics simulations produce huge datasets of temporal sequences of molecules. It is of interest to summarize the shape evolution of the molecules in a succinct, low-dimensional representation. However, Euclidean techniques such as principa... Read More about Principal nested shape space analysis of molecular dynamics data.

Tios: The Internet of Simulations. Turning Molecular Dynamics into a Data Streaming Web Application (2019)
Journal Article
Meletiou, A., Gebbie-Rayet, J., & Laughton, C. (2019). Tios: The Internet of Simulations. Turning Molecular Dynamics into a Data Streaming Web Application. Journal of Chemical Information and Modeling, 59(8), 3359-3364. https://doi.org/10.1021/acs.jcim.9b00351

The configuration of most current academic high-performance computing (HPC) resources tends to enforce ways of working with, and thinking about, molecular dynamics (MD) simulations that are not always optimal. For example, when the aim of the simulat... Read More about Tios: The Internet of Simulations. Turning Molecular Dynamics into a Data Streaming Web Application.

CoCo-MD: A Simple and Effective Method for the Enhanced Sampling of Conformational Space (2019)
Journal Article
Shkurti, A., Styliari, I. D., Balasubramanian, V., Bethune, I., Pedebos, C., Jha, S., & Laughton, C. A. (2019). CoCo-MD: A Simple and Effective Method for the Enhanced Sampling of Conformational Space. Journal of Chemical Theory and Computation, 15(4), 2587-2596. https://doi.org/10.1021/acs.jctc.8b00657

© 2019 American Chemical Society. CoCo ("complementary coordinates") is a method for ensemble enrichment based on principal component analysis (PCA) that was developed originally for the investigation of NMR data. Here we investigate the potential of... Read More about CoCo-MD: A Simple and Effective Method for the Enhanced Sampling of Conformational Space.

Experimental study and computational modelling of cruzain cysteine protease inhibition by dipeptidyl nitriles (2018)
Journal Article
Dos Santos, A. M., Cianni, L., De Vita, D., Rosini, F., Leitão, A., Laughton, C. A., …Montanari, C. A. (2018). Experimental study and computational modelling of cruzain cysteine protease inhibition by dipeptidyl nitriles. Physical Chemistry Chemical Physics, 20(37), 24317-24328. https://doi.org/10.1039/c8cp03320j

Chagas disease affects millions of people in Latin America. This disease is caused by the protozoan parasite Trypanossoma cruzi. The cysteine protease cruzain is a key enzyme for the survival and propagation of this parasite lifecycle. Nitrile-based... Read More about Experimental study and computational modelling of cruzain cysteine protease inhibition by dipeptidyl nitriles.

In Silico Screening for Solid Dispersions: The Trouble with Solubility Parameters and χFH (2018)
Journal Article
Turpin, E. R., Taresco, V., Al-Hachami, W. A., Booth, J., Treacher, K., Tomasi, S., …Garnett, M. C. (2018). In Silico Screening for Solid Dispersions: The Trouble with Solubility Parameters and χFH. Molecular Pharmaceutics, 15(10), 4654-4667. https://doi.org/10.1021/acs.molpharmaceut.8b00637

© Copyright 2018 American Chemical Society. The problem of predicting small molecule-polymer compatibility is relevant to many areas of chemistry and pharmaceutical science but particularly drug delivery. Computational methods based on Hildebrand and... Read More about In Silico Screening for Solid Dispersions: The Trouble with Solubility Parameters and χFH.

Development of a series of bis-triazoles as G-quadruplex ligands (2017)
Journal Article
Saleh, M., Laughton, C. A., Bradshaw, T. D., & Moody, C. J. (in press). Development of a series of bis-triazoles as G-quadruplex ligands. RSC Advances, 7, https://doi.org/10.1039/c7ra07257k

Maintenance of telomeres – specialized complexes that protect the ends of chromosomes – is provided by the enzyme complex telomerase, which is a key factor that is activated in more than 80% of cancer cells, but absent in most normal cells. Targeting... Read More about Development of a series of bis-triazoles as G-quadruplex ligands.

Unveiling a novel transient druggable pocket in BACE-1 through molecular simulations: conformational analysis and binding mode of multisite inhibitors (2017)
Journal Article
Di Pietro, O., Juarez-Jimenez, J., Munoz-Torrero, D., Laughton, C. A., & Luque, F. J. (2017). Unveiling a novel transient druggable pocket in BACE-1 through molecular simulations: conformational analysis and binding mode of multisite inhibitors. PLoS ONE, 12(5), Article e0177683. https://doi.org/10.1371/journal.pone.0177683

The critical role of BACE-1 in the formation of neurotoxic ß-amyloid peptides in the brain makes it an attractive target for an efficacious treatment of Alzheimer’s disease. However, the development of clinically useful BACE-1 inhibitors has proven t... Read More about Unveiling a novel transient druggable pocket in BACE-1 through molecular simulations: conformational analysis and binding mode of multisite inhibitors.

Rapid nano-gram scale screening method of micro-arrays to evaluate drug-polymer blends using high-throughput printing technology (2017)
Journal Article
Taresco, V., Louzao, I., Scurr, D. J., Turpin, E. R., Laughton, C. A., Alexander, C., …Garnett, M. (in press). Rapid nano-gram scale screening method of micro-arrays to evaluate drug-polymer blends using high-throughput printing technology. Molecular Pharmaceutics, 14(6), https://doi.org/10.1021/acs.molpharmaceut.7b00182

A miniaturized, high-throughput assay was optimized to screen polymer-drug solid dispersions using a 2-D Ink-jet printer. By simply printing nanoliter amounts of polymer and drug solutions onto an inert surface, drug:polymer micro-dots of tunable com... Read More about Rapid nano-gram scale screening method of micro-arrays to evaluate drug-polymer blends using high-throughput printing technology.

New N-acyl amino acid-functionalized biodegradable polyesters for pharmaceutical and biomedical applications (2016)
Journal Article
Taresco, V., Suksiriworapong, J., Styliari, I. D., Argent, R. H., Swainson, S. M., Booth, J., …Garnett, M. C. (in press). New N-acyl amino acid-functionalized biodegradable polyesters for pharmaceutical and biomedical applications. RSC Advances, 6(111), 109401-109405. https://doi.org/10.1039/C6RA21464A

A novel class of biodegradable polyesters has been generated by coupling poly(glycerol adipate) with N-acyl aromatic amino acids. This new set of polymers from this highly versatile polymeric platform may offer unprecedented new opportunities to prod... Read More about New N-acyl amino acid-functionalized biodegradable polyesters for pharmaceutical and biomedical applications.

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.