Support for the UKCP consortium
Lead Research Organisation:
King's College London
Department Name: Physics
Abstract
Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
Organisations
People |
ORCID iD |
| Carla Molteni (Principal Investigator) |
Publications
Crnjar A
(2021)
A Single Mutation in the Outer Lipid-Facing Helix of a Pentameric Ligand-Gated Ion Channel Affects Channel Function Through a Radially-Propagating Mechanism.
in Frontiers in molecular biosciences
Crnjar A
(2021)
Cholesterol content in the membrane promotes key lipid-protein interactions in a pentameric serotonin-gated ion channel.
in Biointerphases
Crnjar A
(2019)
Mutagenesis computer experiments in pentameric ligand-gated ion channels: the role of simulation tools with different resolution.
in Interface focus
Crnjar A
(2019)
Trans- Cis Proline Switches in a Pentameric Ligand-Gated Ion Channel: How They Are Affected by and How They Affect the Biomolecular Environment.
in The journal of physical chemistry letters
Fulford M
(2019)
DeepIce: A Deep Neural Network Approach To Identify Ice and Water Molecules.
in Journal of chemical information and modeling
Maschio MC
(2021)
Proline isomerization effects in the amyloidogenic protein ß2-microglobulin.
in Physical chemistry chemical physics : PCCP
Nin-Hill A
(2021)
Photopharmacology of Ion Channels through the Light of the Computational Microscope.
in International journal of molecular sciences
Shi J
(2022)
Investigating the quasi-liquid layer on ice surfaces: a comparison of order parameters.
in Physical chemistry chemical physics : PCCP
Steinmark IE
(2020)
Time-Resolved Fluorescence Anisotropy of a Molecular Rotor Resolves Microscopic Viscosity Parameters in Complex Environments.
in Small (Weinheim an der Bergstrasse, Germany)
| Description | We have been calculating the optical properties of BODIPY-based molecular rotors with first principles and QMMM methods to assess their potential as fluorescent viscosity and temperature sensors (when functionalized in specific ways). We have also studied a green fluorescent protein dimer proposed as a new homoFRET (Förster Resonance Energy Transfer) standard to investigate interactions between proteins in living cells. We have investigated the effects of trans-cis proline switches in biomolecules, specifically in relation to the gating of ligand-gated ion channels (in particular the serotonin-activated 5-HT3 receptor) and the aggregation of the protein beta2 microglobulin involved in dialysis-related amyloidosis. We have studied of the lipid membrane-protein interface, including mutation effects, in the 5-HT3 receptor. We have assessed the interaction of the polyphenol ellagic acid and DNA in different solvents to get insights useful for the process DNA extraction processes from trees; wood DNA may show fingerprints of past climate events. We have been evaluating the interaction of polyphenolic metabolites derived from the consumption of berries with oestrogen receptor alpha; this is a preliminary study to test the molecular basis of the alleged benefits of berries and cocoa on the cardiovascular health. We have explored a variety of ways (order parameters, machine learning) for distinguishing the molecular environment in ice/water systems. We have develop a deep learning approach for this (DeepIce). |
| Exploitation Route | Some of the simulation data (eg on molecular rotors, DNA in trees, polyphenols, ion channels) are directly related to experiments and are meant to help interpret experimental data and guide future experimental explorations. The DeepIce deep learning code is available. It has been used by undergraduate students for project work. |
| Sectors | Chemicals,Electronics,Pharmaceuticals and Medical Biotechnology |
| URL | https://www.ukcp.ac.uk/ |
| Description | This grant was part of a large consortium containing 23 different nodes (university departments) led by Prof. Matt Probert at the University of York. Please see the overview and impact summary of EPSRC Grant EP/P022561/1. The resources also help train PhD and Master students in simulations of biological systems and materials going to a variety of career, from academia to data science. |
| First Year Of Impact | 2021 |
| Sector | Chemicals,Education,Environment,Pharmaceuticals and Medical Biotechnology |
| Impact Types | Societal,Economic |
| Title | DeepIce |
| Description | Deep Neural Network for identifying the phase of water and ice molecules |
| Type Of Material | Computer model/algorithm |
| Year Produced | 2019 |
| Provided To Others? | Yes |
| Impact | This is useful as an example of applying deep neural networks to distinguish structurally different molecular environments. |
| URL | https://github.com/mfulford/DeepIce |
| Title | Localized soft vibrational modes and coherent structural phase transformations in rutile TiO2 nanoparticles under negative pressure |
| Description | This repository contains: 1.Dataset of phonon calculations of TiO2 nanoprticles with various radius at negative pressure 2.The corresponding codes to generate dynamical matrix of nanoparticles based on DFT calculations of bulk dynamical matrix and the corresponding DFT input files. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2022 |
| Provided To Others? | Yes |
| Impact | The database provides codes and application data related to new efficient methodology to construct the dynamical matrices of nanoparticles based on density functional theory calculations for the bulk. |
| URL | https://zenodo.org/record/6771114 |
| Title | Potential energy surfaces, absorption and emission spectra of three fluorescent molecular rotors |
| Description | Ground and excited state potential energy surfaces and absorption and emission spectra of BODIPY-C10, BODIPY-Cyclopropyl-A and BODIPY-Cyclopropyl-B, calculated using the Gaussian 09 Code. Type of data: Quantum mechanical simulation files. Data set for " Cyclopropyl Substituents Transform the Viscosity-Sensitive BODIPY Molecular Rotor into a Temperature Sensor" |
| Type Of Material | Database/Collection of data |
| Year Produced | 2021 |
| Provided To Others? | Yes |
| Impact | This dataset, based on density functional theory and time-dependent density functional theory, is part of a joint experimental and computational study to develop BODIPY-based temperature sensors through functionalization of a molecular rotor. The study is published in https://doi.org/10.1021/acssensors.0c02275 |
| Title | Potential energy surfaces, absorption and emission spectra of three fluorescent molecular rotors |
| Description | Ground and excited state potential energy surfaces and absorption and emission spectra of BODIPY-C10, BODIPY-Cyclopropyl-A and BODIPY-Cyclopropyl-B, calculated using the Gaussian 09 Code.Type of data: Quantum mechanical simulation files |
| Type Of Material | Database/Collection of data |
| Year Produced | 2021 |
| Provided To Others? | Yes |
| Impact | The data support the development of molecular rotors for sensing temperature. |
| URL | https://kcl.figshare.com/articles/dataset/Potential_energy_surfaces_absorption_and_emission_spectra_... |
| Title | Simulation data I (molecular dynamics) for 'Trans-Cis Proline Switches in a Pentameric Ligand-Gated Ion Channel - How They Are Affected by and How They Affect the Biomolecular Environment' |
| Description | Pentameric ligand-gated ion channels (pLGICs) are important neuroreceptors, embedded in neuronal membranes, that mediate fast synaptic transmission. The molecular details of their working mechanisms have still to be fully unravelled due to their complexity and limited structural information available. Here we focus on a potential molecular switch in a prototypical pLGIC, the serotonin-activated 5-HT3 receptor, consisting of the trans-cis isomerization of a proline at the interface between the extracellular and transmembrane domain. We investigate this switch within the receptor with molecular dynamics (data reported here) and metadynamics simulations. The molecular dynamics simulations were performed for four different models, named 5Trans (with Pro281 in the trans conformation for all the five subunits), 3Cis (with Pro281 in the cis conformation in subunits 1, 3 and 4), 5Cis (with the five Pro281 in cis), and 5Trans5Cis (with the five Pro281 in trans and the five Pro274 in cis). |
| Type Of Material | Database/Collection of data |
| Year Produced | 2020 |
| Provided To Others? | Yes |
| Impact | These data show molecular dynamics simulations of a pentameric ligand gated ion channel embedded in a lipid bilayer and provide useful information for setting up simulations of similar systems within the research group and outside. |
| Title | Simulation data II (metadynamics) for 'Trans-Cis Proline Switches in a Pentameric Ligand-Gated Ion Channel - How They Are Affected by and How They Affect the Biomolecular Environment' |
| Description | Pentameric ligand-gated ion channels (pLGICs) are important neuroreceptors, embedded in neuronal membranes, that mediate fast synaptic transmission. The molecular details of their working mechanisms have still to be fully unravelled due to their complexity and limited structural information available. Here we focus on a potential molecular switch in a prototypical pLGIC, the serotonin-activated 5-HT3 receptor, consisting of the trans-cis isomerization of a proline at the interface between the extracellular and transmembrane domain. We investigate this switch within the receptor with metadynamics simulations (data reported here) and molecular dynamics. The metadynamics simulations concern the isomerisation process of Pro281 in subunit 3. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2020 |
| Provided To Others? | Yes |
| Impact | These data show how to carry out an enhanced sampling study with metadynamics of proline isomerization in a complex biomolecular environment, useful for computational scientists interested in similar systems. |
| Title | Simulation data for "A Single Mutation in The Outer Lipid-Facing Helix of a Pentameric Ligand-Gated Ion Channel Affects Channel Function through a Radially-Propagating Mechanism" |
| Description | Pentameric ligand-gated ion channels (pLGICs) mediate fast synaptic transmission and are crucial drug targets. Their gating mechanism is triggered by ligand binding in the extracellular domain that culminates in the opening of a hydrophobic gate in the transmembrane domain. This domain is made of four a-helices (M1 to M4). Recently the outer lipid-facing helix (M4) has been shown to be key to receptor function, however its role in channel opening is still poorly understood. It could act through its neighbouring helices (M1/M3), or via the M4 tip interacting with the pivotal Cys-loop in the extracellular domain. Mutation of a single M4 tyrosine (Y441) to alanine renders one pLGIC - the 5-HT 3A receptor - unable to function despite robust ligand binding. Using Y441A as a proxy for M4 function, we here predict likely paths of Y441 action using molecular dynamics, and test these predictions with functional assays of mutant receptors in HEK cells and Xenopus oocytes using fluorescent membrane potential sensitive dye and two-electrode voltage clamp respectively. We show that Y441 does not act via the M4 tip or Cys-loop, but instead connects radially through M1 to a residue near the ion channel hydrophobic gate on the pore-lining helix M2. This demonstrates the active role of the M4 helix in channel opening. Molecular dynamics trajectories and data are provided. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2021 |
| Provided To Others? | Yes |
| Impact | Simulation data for a joint experimental and computational study to investigated the effect of a mutation in the lipid membrane facing M4 helix in the 5-HT3 receptor, a serotonin gated ion channel. The study is published in https://doi.org/10.3389/fmolb.2021.644720 |
| Title | Simulation data for "Cholesterol Content in the Membrane Promotes Key Lipid-Protein Interactions in a Pentameric Serotonin-Gated Ion Channel" |
| Description | We investigate, by means of molecular dynamics simulations, the behaviour of the lipid membrane at the interface with the pentameric ligand-gated ion channel 5-HT3 receptor. Three lipid compositions are studied, spanning different concentrations of the phospholipids POPC and POPE and of cholesterol, hence a range of viscosities. A variety of lipid interactions and persistent binding events to different parts of the receptor are revealed in the investigated models. Some of these events result in lipid intercalation within the transmembrane domain, while certain lipids reach out to protein key sections for signal transmission and receptor activation, such as the Cys-loop and the M2-M3 loop. In particular, phospholipids are revealed to play an important role in these interactions, potentially providing a bridge between these two structures. A higher cholesterol content appears to promote lipid persistent binding to the receptor. Molecular dynamics trajectories and data are provided. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2020 |
| Provided To Others? | Yes |
| Impact | Simulation data supporting the paper : Biointerphases 15, 061018 (2020); https://doi.org/10.1116/6.0000561 on the effects of lipid composition on the interface between the membrane and a pentameric serotonin-gated ion channel, the 5-HT3 receptor. |
| URL | https://librarysearch.kcl.ac.uk/primo_library/libweb/action/dlDisplay.do?&docId=44KCL_ALEPH_RDM_DS06... |
| Title | Simulation data for "Time-resolved fluorescence anisotropy and molecular dynamics analysis of a novel GFP homo-FRET dimer" |
| Description | In this work, molecular dynamics simulations were carried out to study the dynamical properties of a monomer and a dimer of green fluorescent protein (GFP) in order to provide an in-silico validation of FRET (Förster resonance energy transfer) efficiency, calculated from the fit of the fluorescence anisotropy decays with a stretched exponential decay model. An excellent agreement was found between model and experiments. Dynamical insights on the dimer linker and on the protein tumbling were also obtained from the simulations. The molecular dynamics data are provided here. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2020 |
| Provided To Others? | Yes |
| Impact | These data complement and support experiments published jointly published in DOI:https://doi.org/10.1016/j.bpj.2020.11.2275 |
| Title | Simulation data for 'Investigating the quasi-liquid layer on ice surfaces: a comparison of order parameters' |
| Description | Ice surfaces are characterized by pre-melted quasi-liquid layers (QLLs) which mediate both crystal growth processes and interactions with external agents. Understanding QLLs at the molecular level is necessary to unravel the mechanisms of ice crystal formation. Computational studies of the QLLs heavily rely on the accuracy of the methods employed for identifying the local molecular environment and arrangements, discriminating solid-like and liquid-like water molecules. We compared the results obtained using different order parameters to characterize the QLLs on hexagonal ice (Ih) and cubic ice (Ic) model surfaces investigated with molecular dynamics (MD) simulations (Surf_MD_data reported here) in a range of temperatures. To evaluate the threshold between distinguishing ice and water, we also performed MD simulations in the bulk systems of ice and water (Bulk_MD_data reported here). For the classification task, in addition to the traditional Steinhardt order parameters in different flavours, we select an entropy fingerprint and a deep learning neural networks approach (DeepIce), which are conceptually different methodologies. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2022 |
| Provided To Others? | Yes |
| Impact | The data provide information useful to select appropriate order parameters to describe mixed phase water-based systems. |
| URL | https://kcl.figshare.com/articles/dataset/Simulation_data_for_Investigating_the_quasi-liquid_layer_o... |
| Title | Simulation data for Simulation data for "Extraction and high-throughput sequencing of oak heartwood DNA: assessing the feasibility of genome-wide DNA methylation profiling" |
| Description | Studies of the methylation state of DNA preserved in oak heartwood can help identify epigenetic tree ring features informing on past environmental conditions. Heartwood contains little DNA; large amounts of phenolic compounds are known to hinder the preparation of high-throughput sequencing libraries. To complement experiments, we simulated the interaction of double-stranded DNA (dsDNA) with a potential PCR inhibitor, the phenolic compound ellagic acid, by molecular dynamics and metadynamics tec |
| Type Of Material | Database/Collection of data |
| Year Produced | 2021 |
| Provided To Others? | Yes |
| Impact | This dataset has contributed to provide an understanding at the molecular level of the interaction of double-stranded DNA (dsDNA) with a potential PCR inhibitor, the phenolic compound ellagic acid within a collaboration to extract and investigate DNA from heartwood. The join experimental and computational study has been published in https://doi.org/10.1371/journal.pone.0254971 |
| URL | https://doi.org/10.18742/RDM01-502 |