People news

Congratulations to…

  • Louis Sayer, who graduated with a L4 project dedicated to profiling molearn, our neural network trainable with protein molecular dynamics conformations.
  • Saabir Petker, who graduated with a L4 project on assessing the peformance of JabberDock, our protein-protein docking engine
  • Hao Man who, under the co-supervision of Prof. Martin Cann in Durham’s Department of Biosciences, obtained a postgraduate degree in data science with a project dedicated to the prediction of lysine carbamylation sites using neural networks.

Welcome to…

  • Ella Finley and Victoria Liu who, sponsored by the BiSCOP and MosMed CDTs, start a PhD on the characterization of protein carbamylation sites under the main supervision of Prof. Martin Cann.
  • Ryan Zhu who, under the main supervision of Dr. Antonia Mey at the University of Edinburgh, starts a PhD funded by Redesign Science on the usage of generative models to characterize protein conformational spaces.
  • Hannah Lydon, starting a L4 project on the refinement of docking poses generated by JabberDock
  • Cameron Stewart, starting a L4 project on the usage of molearn to predict transition states between protein conformations.

Conferences and Workshops

This will be a busy month for the group… let us know if you want to meet up!

Matteo, Sam and Cameron will attend the CCPBioSim conference in Edinburgh (6-8 June). The conference will be followed by a MD+ML workshop, where Matteo will show how to use the MDAnalysis and sklearn Python packages to characterize molecular dynamics simulations.

Matteo will then travel to Erice for the MolSim22 conference (25-29 June) and then, along with Sam, to Barcelona for the MMSML Workshop (14-16 July).

Finally, Josh will attend the CCP5 Summer School in Durham (17-28 July).

PhD studentship available

A fully funded studentship in the area of machine learning for computational biophysics is available in our group, starting October 2022.

All living organisms contain millions of proteins; biopolymers that fold into three-dimensional biologically active structures playing a vital role in the regulation of life and diseases. Research has seen a lot of focus on determining the atomic structure of different proteins. However, the flexible movement of these biopolymers plays a crucial role in their biological (mal)function.

In recent years, machine learning has been revolutionizing the way we interpret data in many scientific areas. For example, the deep neural network AlphaFold2 can predict the 3-dimensional structures of proteins, whose shape is not known experimentally. In our research, we have designed a deep neural network that can also learn an ensemble of structures of specific proteins from molecular simulations. This project builds upon this breakthrough.

In collaboration with the Willcocks group (Department of Computer Science), the student will develop a general neural network capable of learning and predicting the dynamics of any protein. The neural network will be trained with existing and new data you will produce from molecular dynamics simulations. Applications of this work are vast, ranging from understanding the effect of genetic mutations in cancers to informing the design of proteins to carry out a desired function.

Do you have a background in physics, computer science, chemistry, biology, or related discipline, and are keen to develop your computational skills to address biomolecular problems? Then please direct any informal enquiries to Matteo ( More information on the application process can be found here. Applications will be considered until the 3rd April.

Making biomolecular modelling slightly less fiddly

Are you thinking about writing a Python program to load a bunch of PDB files and measure some of their properties (CCS, interatomic distances, solvent-accessible paths, SAXS, …)? Perhaps you would like to move a bunch of structures around to form a complex in your integrative modelling pipeline, where every subunit may take several conformations? Or how about creating bead models of electron density maps, or the opposite? Do you find it fiddly? We did too, this is why we have created Biobox!

Biobox is a Python package that caters for virtually all our biomolecular modelling needs. Basically every publication we ever produced in the last 8 years did, in a way or another, feature Biobox. Now we are making it public, hopefully you will find as helpful for your work as it was for ours! We have put information about it here, including API and a Jupyter notebook demonstrating its main features.

People news

Congratulations to….

  • Lucas Rudden, who is now a doctor after having successfully defended his thesis titled “The Impact of Dynamics in Protein Assembly“. Lucas finished with a bang, by winning two prizes for his work: the BSI Thesis Prize and the Departmental Winton Prize. He has now moved to the group of Prof. Patrick Barth in EPFL as PDRA.
  • Venkat Ramaswamy, who started his new job as researcher in Cresset after having spent two years with us as PDRA, developing machine learning methods to sample protein conformational space.
  • Lucy Vost, who successfully completed her L4 project on molecular dynamics coupled with machine learning, and in October will start her doctoral studies in Computational Discovery at the University of Oxford.

Welcome to…

  • Cameron McAllister, who joins us as PhD student within the SOFI2 CDT programme. Cameron, co-supervised by Dr. Beth Bromley and Prof. Kevin Weatherhill, will develop molecular modelling methods to predict proteins’ Enhanced Acoustic Raman (EAR) spectra.
  • Louis Sayer, joining us for the 2021/22 L4 project on machine learning protein conformational spaces with molearn.
  • Saabir Petker, joining us for 2021/22 L4 project on protein-protein docking with JabberDock.
  • Charles Brown, doing an 8 week-long internship with us. In collaboration with Prof. Martin Cann, Charlie will develop a computational pipeline to investigate lysine carbamylation.

A Neural Network To Predict How Proteins Change Shape

Proteins shape is constantly changing in response to a variety of biological processes. For example, a protein may be folded into a compact shape and then open up to grab a molecule such as a drug. Predicting what change occurs when you observe proteins behave in an experiment can be difficult. This is because intermediates between two states are by their nature transient, and therefore difficult to observe.

In collaboration with Chris Willcocks in Durham University, We have trained a neural network on protein shapes generated by molecular dynamics simulations, and then asked it to predict possible protein intermediate conformations. We demonstrated that the system can generate conformations that are both physically plausible and close enough to known intermediates. The convolutional architecture of our neural network can accommodate any protein, without the need of being customised. One added advantage that comes with this architecture is transfer learning, which can assist with training on a sparse dataset by first exposing the neural network to a related richer dataset.

This blog post was written with the help of a neural network, that also decided on the title.

V.K. Ramaswamy, S.C. Musson, C.G. Willcocks, M.T. Degiacomi. Learning protein conformational space with convolutions and latent interpolations. Physical Review X 11

Integral membrane protein docking

JabberDock, our protein-protein docking algorithm, has been extended to handle integral membrane proteins. We have created a benchmark set featuring 20 diverse dimers, and used it to demonstrate that our method yields an acceptable solution in its top 10 candidates in 75% of cases.

The first application of JabberDock for membrane proteins has been in the scope of a collaboration with the Kukura group at the University of Oxford. Our models of the protein bo3 oxidase have contributed demonstrating that mass photometry, a novel label-free single molecule technique to measure the mass of biomolecules, can interrogate membrane proteins.

Ray tracing + protein docking = protein tracing

Protein docking essentially involves taking the atomic structure of two proteins, generating a collection of possible molecular arrangements, and scoring their quality to determine the best one. However, the vast majority of arrangements will feature proteins that either overlap of do not touch. As these cases are uninteresting, generating them and assessing their quality is a waste of time.

Enter shape tracing. In collaboration with the Chris Willcocks group in Durham’s Computer Science Department (in particular, shout-out to Adam Leach), we combine our protein volumetric representation (STID maps) with a generalisation of ray racing capable of detecting the collision of arbitrary three-dimensional shapes.

This enables us to very quickly generate arrangements of proteins that are in contact but do not overlap, speeding up the search for the most suitable model.

A. Leach, L.S.P. Rudden, S. Bond-Taylor, J.C. Brigham, M.T. Degiacomi, C.G. Willcocks (2020). Shape tracing: An extension of sphere tracing for 3D non-convex collision in protein docking, 2020 IEEE 20th International Conference on Bioinformatics and Bioengineering (BIBE)

Welcome Lucy!

Lucy, Physics student in Durham, joins us for her Masters project. She will work on using molecular simulations and convolutional neural networks to sample protein conformational spaces.

Mass spectrometry, structural biology and computational methods: 3 articles!

This week we celebrate the publication of three articles in Analytical Chemistry!

How well do we understand different aspects of native mass spectrometry? And their relationships?

In the scope of the EU COST Action BM1403 on Native MS and Related Methods for Structural Biology, we have contributed to the redaction of two articles. These review existing methods and software to analyse and interpret native mass spectrometry data, and  highlight state of the art and current challenges in the area. We hope these works will stimulate discussions within the community, and serve as help for newcomers to the area

MS_erik_michaelIn related news, in collaboration with Michael Landreh (Karolinska Instituet) and Erik Marklund (Uppsala University) we have figured out that ion mobility can tell more than one would think about the shape of protein complexes. Coupling collision cross section and mass measurements with protein databank searches, we have shown that it is possible to determine whether a protein complex is prolate (like a cigar) or oblate (like a disk).

M. Landreh et al. (2020). Predicting the shapes of protein complexes through collision cross section measurements and database searches, Analytical Chemistry