Highlights
Generating Protein Folding Trajectories Using Contact-Map-Driven Directed Walks
Journal of Chemical Information and Modeling
With the advent of AlphaFold, predicting the folded structure of any given protein has become much easier. And yet, AlphaFold doesn't tell you anything about how exactly the protein folds: what intermediate states, if any, does it visit before folding; what about misfolded structures; and what is the kinetic of the folding process? To answer any of these questions, we need to take a step back and think of clever ways in which we can avoid the so-called timescale problem – i.e., the fact that protein folding usually happens on timescale far beyond the reach of what we can simulate by, for instance, classical molecular dynamics. This work, led by Scott Habershon (the oldest and wisest member of Warwick Catch) and Ziad Fakhoury (a PhD student within the HetSys CDT), puts forward an ingenious methodology that leverages "simple" graphs to gain insight into the folding mechanism. This is the start of a long road – here, we used a simple model protein, but would we be able to apply this to big proteins as well? Stay tuned! Meanwhile, have a look at the paper online or grab a pdf here.
Understanding the Emergence of the Boson Peak in Molecular Glasses
Nature Communications
The boson peak is a fundamental, very unique feature of glassy materials. As such, people have been arguing about the actual origin of the boson peak for many years indeed. In this work, spearheaded by Klaas Wynne (Glasgow University) and featuring molecular simulations by our very own Trent Barnard (amongst a real arsenal of other techniques), we pinpoint the emergence of specific structural features as the motivation behind the occurrence of the boson peak – at least in this class of molecular glasses! Understanding the boson peak in general terms is still very much an ongoing quest, but with this work, now published in Nature Communications we have provided an important piece of the puzzle. Check it out online or grab a pdf here.
Levering Genetic Algorithms to Maximise the Predictive Capabilities of the SOAP Descriptor
Molecular Systems Design and Engineering
In this collaboration with AstraZeneca, James Darby in Cambridge, and Warwick's Albert Bartók-Partay, we explore the capabilities of genetic algorithms (GAs) when used to optimise the hyperparameters of the popular SOAP descriptor. SOAPs are a commonly used method to encode atomic local environments, with good performance over a wide range of materials. We show that by using our genetic algorithm package (available at https://github.com/gcsosso/SOAP_GAS) the predictive capabilities of SOAPs are improved for a variety of datasets. There were notable improvements when predicting the solubility of molecules in a prototypical molecular database for drug design, and when predicting the polarizability of the QM7b dataset. We also showcase the improvements on both optimisation speed and quality of our GA when compared to the more commonly used random grid search. Have a look at the paper online or grab a pdf here.
Minimalistic ice recrystallisation inhibitors based on phenylalanine
Chemical Communications
The second instalment of our work amino acids, this paper introduces phenylalanine as a minimalistic, yet potent, ice growth inhibitor. We explore the structure-function relationships in a panel of phenylalanine derivatives, revealing the importance of both hydrophobic and hydrophilic regions and a possible role of self-assembly in ice growth inhibition. Have a look at the paper online or grab a pdf here.
The role of structural order in heterogeneous ice nucleation
Chemical Science
It took some six years for this paper to eventually see the light of day - but it was worth it.
Titled: "The role of structural order in heterogeneous ice nucleation" and published in Chemical Science, this work is a testament to a massive collaborative effort that involved myself (when I was working Angelos Michaelides at UCL, now Cambridge) and a stellar team at the Max Plank in Mainz (Ellen Backus is now in Wien), in addition to our very own Tom Whale (in Leeds at the time).
In a nutshell, with this paper we tried to look at the same thing, cholesterol, in different forms, from crystals to more-or-less disordered monolayers, and get an idea of how well these different forms nucleate ice. This is important for a number of reasons: a fundamental one is that it is usually very hard to isolate the effect of structural disorder on ice nucleation. A more practical one is that cholesterol is part of our own cell membranes - hence it is quite key to investigate what does it do to water and ice. Yet another piece of the puzzle, we think, but this is a long road. Have a look at the paper online or grab a pdf here.
How do Interfaces Alter the Dynamics of Supercooled Water?
Nanoscale
It was somewhere in Switzerland (some 10 years ago?), during a conference featuring excellent food, loads of snow, some newly found colleagues who I still call friends and - incidentally - some interesting science as well, when the concept of dynamical heterogeneity (DH) was first pitched to me (by a certain Emanuela del Gado, now at Georgetown University). This paper, to which I only marginally contributed to, represents the very latest chapter of my DH saga (very much still ongoing, fear not!). I am very grateful to Piero (Gasparotto, who led this), Martin (Fitzner), Steve (Cox) and the ICE group at Cambridge for doing all the hard work and for persevering along what was a fairly rocky road. But we did it, and I love this work. It poses interesting questions for the future, and I can only hope to be a part of the team that is going to be answering those in the near future. DH is fun. And it matters. And it also allows for very snazzy figures. Have a look at the paper online or grab a pdf here
Ice Recrystallization Inhibition by Amino Acids: The Curious Case of Alpha- and Beta-Alanine
The Journal of Physical Chemistry Letters
In this work, we report the discovery that the amino acid alpha-alanine - a natural building block of proteins - can inhibit ice recrystallisation (growth) at low millimolar concentrations. To understand how this process works at the molecular level, we combined experimental and computational approaches to measure and simulate the growth of ice in the presence of alpha-alanine or beta-alanine. Despite having the same atomic composition as alpha-alanine, beta-alanine does not inhibit ice growth, making for a puzzling case study on this topic. We traced the inhibition activity of alpha-alanine to its ability to resist becoming overgrown by the growing ice front, characterised by its unfavourable fit within the ice lattice. These results represent a key contribution to our growing understanding of ice recrystallisation inhibition and may translate into improved cryopreservation practices. Have a look at the paper online or grab a pdf here.
Lipid Bilayers as Potential Ice Nucleating Agents
Physical Chemistry Chemical Physics
This paper is about whether cellular membranes could be responsible for facilitating the ice nucleation process, and what characteristics would make them good or bad ice nucleating agents. We simulated several phospholipids and lipopolysaccharide bilayers at the interface with supercooled liquid water. A bilayer's ability to act as an ice nucleating agent is complex, with both chemical and structural factors of relevance. Such bilayers appear to act as ice nucleating agents, although other impurities likely also play a role in initiating extracellular ice nucleation. These findings represent a first attempt to pinpoint the origin of extracellular ice nucleation, with important implications for the cryopreservation process. Have a look at the paper online or grab a pdf here.
Recovering Local Structure Information from High-Pressure Total Scattering Experiments
Journal of Applied Crystallography
This work is all about disordered phases at very high pressures. Specifically, a dream team of experimentalists (including our very own Mark Senn from Warwick Chemistry) came up with a clever way to subtract the pair correlation functions of the pressure-transmitting medium (that is, the liquid that is used in experiments to transmit the applied pressure to the actual sample) from those of the material of interest. We only played a little role in this, by providing the pair correlation functions of methanol/ethanol mixtures via molecular dynamics simulations at various pressures. It was great to see our numbers put into the experimental context! Have a look at the paper online or grab a pdf here.
The Seven Deadly Sins: When Computing Crystal Nucleation Rates, the Devil is in the Details
Journal of Chemical Physics
In this paper (chosen as an "Editor's Pick"), we discuss the many different pitfalls that computation of crystal nucleation rates can fall into. Perhaps unsurprisingly, there are rather a lot! Hopefully these are lessons that we all (ourselves included) can learn from. Have a look at the paper online or grab a .pdf.
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DImEnsION @ Warwick focuses onMolecular Simulations of Disordered Systems and Phase Transitions.
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