Categories
computing molecular dynamics publication research

New Publication: Predicting affinities for peptide transporters

PepT1 is a nutrient transporter found in the cells that line your small intestine. It is not only responsible for the uptake of di- and tai-peptides, and therefore much of your dietary proteins, but also the uptake of most β-lactam antibiotics. This serendipity ensures that we can take (many of) these important drugs orally. Our […]

Categories
publication research

New Publication: The Extra-Cellular Domain of PepT1 and PepT2

PepT1 is a nutrient transporter found in the cells that line your small intestine. It is not only responsible for the uptake of di- and tai-peptides, and therefore much of your dietary proteins, but also the uptake of most β-lactam antibiotics. This serendipity ensures that we can take (many of) these important drugs orally. Our […]

Categories
molecular dynamics publication research

New Publication: Alchembed

In much of my research I’ve looked at how proteins embedded in cell membranes behave. An important part in any simulation of a membrane protein is, obviously, putting it into a model membrane, often a square patch of several hundred lipid molecules. This is surprisingly difficult: although a slew of methods have been published, none of […]

Categories
publication

New publication: Nothing to Sneeze At – A Dynamic and Integrative Computational Model of an Influenza A Virion

In this paper we show how we built and then simulated a model of the influenza A virion. Rather than model every atom of every lipid, a “coarse-grained” representation (MARTINI) is instead used which replaces roughly every four atoms by a single coarse-grained bead. Microsecond simulations then start to give us insight into how the […]

Categories
publication research

New publication: Gating Topology of the Proton-Coupled Oligopeptide Symporters

[Could not find the bibliography file(s) This paper [BIBCITE%%0%] is the result of a large collaboration between several groups. Since all the current crystal structures of peptide transporters are open to the cytoplasm (and hence closed to the periplasm), we wanted to investigate what bacterial peptide transporters (here PepTSo [BIBCITE%%1%] and PepTSt [BIBCITE%%2%]) looked like when they were open to the periplasm. […]

Categories
publication research

New publication: Insights into the structural nature of the transition state in the Kir channel gating pathway.

[Could not find the bibliography file(s) We recently examined how Kir1.1, an inwardly-rectifying potassium channel that is found in the kidneys, opens and closes in response to being stimulated by changes in pH or the presence of absence of PIP2, a signalling lipid [BIBCITE%%3%]. The key result of that paper was that we could identify several […]

Categories
publication research

New Publication: State-Dependent Network Connectivity Determines Gating in a K+ Channel

In an earlier paper we showed that the closed state of Kir1.1, a important potassium ion channel found in the kidneys, was stabilised by a single hydrogen bond. This paper builds on that work by looking for any interactions that stabilise either the open or closed state of the channel by systematically mutating the majority […]

Categories
publication

New Publication: NRas slows the rate at which a model lipid bilayer phase separates

  Here we examine by computer simulation what effect adding a small cell-signalling protein does to a model ternary lipid mixture that has been shown before to phase separate. This paper was presented at the 169th Faraday Discussion meeting in Nottingham in May 2014, the theme of which was Molecular simulations and visualization. We followed […]

Categories
publication research

New Publication: Flexible Gates Generate Occluded Intermediates in the Transport Cycle of LacY

In this paper we examine how the lactose permease, LacY, changes its structure to shuttle molecules of lactose across a cell membrane. The change in conformation is modelled usinga biased computational method called dynamic importance sampling (DIMS) and the results compared to the results of some previously published double electron electron spin resonance (DEER) experiments. […]

Categories
publication research

New Publication: Energetics of Multi-Ion Conduction Pathways in Potassium Ion Channels

Can we predict the conductance of a potassium ion channel from an experimental structure? In this paper we examine the kinetic barriers experienced by potassium ions (and waters) as they move through the narrowest part of two different potassium ion channels. We examine the reproducibility of our results and test the sensitivity of the approach to […]