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Postdoctoral position available

A 2-year PDRA position is available in our group, working on the EPSRC-funded project Software for Experimentally Driven Macromolecular Modelling.

The work will involve development and application of novel integrative modelling methodologies for the study of flexible protein monomers and the prediction of their multimeric arrangement. The position is available from October 2018.  Full information and application form on Durham University vacancies site (job ID: 015726). Contact Matteo matteo.t.degiacomi@durham.ac.uk for informal inquries.

Physics of Life Summer School

This week, Durham University is hosting the Physics of Life Network’s summer schoolNew approaches to biomolecular structure, dynamics and function“. This is an exciting learning and exchange opportunity for researchers having different backgrounds, but a common interest in the life sciences.

Lucas is presenting a poster on his work, aimed at developing novel volumetric representations accurately recapitulating protein intrinsic dynamics.

Think positive about negative

Our article has been just published on PNAS! In this work we study the effect of specific protein-lipid interactions with a palette of techniques featuring  native mass spectrometry, molecular dynamics and channel recording experiments alongside our own structural bioinformatics analysis (on the left in the figure).

news_imageWe found that within membrane proteins there exists a huge amount of variability on the amount of charged amino acids exposed with lipid heads, and identified proteins that may modulate their function via specific pH-modulated interactions with the neighbouring bilayer. This is exemplified by the protein OmpF, a channel that remained open for longer times in the presence POPG lipids under acidic conditions.

So, what about this “think positive about negative” title? This refers to the observation that probing protein-lipid samples with both positive and negative electrospray ionization (the latter not commonly used in the word of native mass spectrometry) can provide precious insights into specific protein-lipid interactions. This actually, half jokingly, almost became the title of the paper!

Reference (currently in online form): Liko, I.,  et al.,  (2018). Lipid binding attenuates channel closure of the outer membrane protein OmpF. PNAS

 

SoftComp conference in Primosten

Matteo attended the joint SoftComp and EUSMI meeting in the beautiful Primosten, Croatia. The meeting brought together theoreticians and experimentalists focussed on the study of soft matter.

2018-05-29-16-32-54_img_7238Matteo presented his work on the integrative modelling of small heat shock proteins assemblies (including the image that is currently the cover of this website), exploiting his methods for protein docking, and interpretation of SAXS and cross-linking data.

New article on super-coarse grain modelling guided by collision cross-section

13361_2018_1974_Figa_HTMLThis work studies the way collision cross-section measurements can guide the modelling of large protein assemblies represented as super coarse-grain objects (i.e. a single big sphere per protein).

We show that there exists a relationship between spheres overlap and collision cross-section that can be leveraged to define modelling restraints on a per-case scenario.

Degiacomi, M.T. On the Effect of Sphere-Overlap on Super Coarse-Grained Models of Protein Assemblies (2018), Journal of the American Mass Spectrometry Society

On a maybe less serious note, this work meets the stringent requirements of the “Palatinate Challenge” set up within Durham University computational chemistry groups.

BSI research lunch

bsiMatteo presented the group’s research at one of the periodic BSI research lunches.  Durham’s Biophysical Research Institute is constituted by researchers with different backgrounds, but a common interest in the life sciences. The periodic research lunches provide an opportunity to get together, discuss in an informal setting, and establish collaborations.

Workshops time!

Lucas attended the “Advanced Methods for the Integration of Diverse Structural Data” workshop in Florence. Lucas says: “The workshop covered the foundations and software associated with widely used and upcoming structual biology techniques; including SAXS, NMR, cryo-EM and crystallography in the context of integrative modelling. The days were jam packed with information, and really enlightened a newly christened biophysist such as myself. And of course, the beautiful city of Florence set the backdrop – with good food and wine, which warmed us up in spite of the cold weather from Siberia!”

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In the meantime, Matteo travelled to the Freie Universität Berlin to attended the workshop “Computer Tutorial in Markov Modeling“. Some excellent work from the the pyEMMA team, really good to learn about what this Python package can do for the interpretation of MD simulations!

New article published on Science!

The article “Structural principles that enable oligomeric small heat-shock protein paralogs to evolve distinct functions” has been published today in Science!

Most proteins assemble into complexes to achieve a specific biological function. In this work, we show how small Heat Shock Proteins assemble selectively according to mechanisms away from the typical shape and charge complementarity, and that this phenomenon might in fact be widespread. Our results indicate an economical mechanism for duplicated proteins to evolve distinct functions: modification of a minimal amount of amino acids, altering protein dynamics but not their structure, allows preventing co-assembly.

This work is the fruit of several years of collaboration between researchers from areas as diverse as molecular and plant biology, molecular dynamics and modelling and crystallography.  For more information, see the University of Oxford blog post.

Georg K. A. Hochberg et al., Structural principles that enable oligomeric small heat-shock protein paralogs to evolve distinct functions, Science, Vol. 359, Issue 6378, pp. 930-935, 2018 [Supplemental data is available here]

New publication: Mineral surface chemistry control for origin of prebiotic peptides

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Our study, in collaboration with Durham and Oxford Earth Sciences departments, has been published in Nature Communications. Herein we demonstrate how, in early Earth conditions, layered double-hydroxides could have adsorbed amino acids, favouring the formation of peptidic bonds. We propose that successive wetting-drying cycles could have enabled the formation of peptidic chains having a length compatible to  that of simple functional proteins.

Erastova, V., Degiacomi, M.T., Fraser, D.G., Greenwell, H.C. (2017). Mineral surface control for origin of prebiotic peptides, Nature Communications.

All datasets related to this work are available here.