Papers by Joshua Berryman
Considerations in experimental and theoretical collision cross-section measurements of small molecules using travelling wave ion mobility spectrometry-mass spectrometry
International Journal of Mass Spectrometry, Dec 1, 2010
Travelling wave ion mobility spectrometry-mass spectrometry (TWIMS-MS) has the capability to sepa... more Travelling wave ion mobility spectrometry-mass spectrometry (TWIMS-MS) has the capability to separate ions based on their mobility through a gas-filled travelling wave (T-wave) device in the presence of a train of transient voltage pulses. By calibration of this device using analytes of previously determined cross-sectional area (from conventional IMS experiments), collision cross-sections of ions can be determined based on their
Journal of Chemical Physics, Aug 9, 2022
Computer Physics Communications, Jul 1, 2014
Advanced Science, Dec 11, 2020
The Journal of Chemical Physics
In order to improve the accuracy of molecular dynamics simulations, classical forcefields are sup... more In order to improve the accuracy of molecular dynamics simulations, classical forcefields are supplemented with a kernel-based machine learning method trained on quantum-mechanical fragment energies. As an example application, a potential-energy surface is generalized for a small DNA duplex, taking into account explicit solvation and long-range electron exchange–correlation effects. A long-standing problem in molecular science is that experimental studies of the structural and thermodynamic behavior of DNA under tension are not well confirmed by simulation; study of the potential energy vs extension taking into account a novel correction shows that leading classical DNA models have excessive stiffness with respect to stretching. This discrepancy is found to be common across multiple forcefields. The quantum correction is in qualitative agreement with the experimental thermodynamics for larger DNA double helices, providing a candidate explanation for the general and long-standing dis...
Machine Learning on a Quantum Hamiltonian shows that DNA is Much Stretchier than Classical Simulations Suggest
Bulletin of the American Physical Society, Mar 15, 2021
nucleation mechanism in melts of short polymer chains under
COVID-19 is primarily known as a respiratory disease caused by the virus SARS-CoV-2. However, neu... more COVID-19 is primarily known as a respiratory disease caused by the virus SARS-CoV-2. However, neurological symptoms such as memory loss, sensory confusion, cognitive and psychiatric issues, severe headaches, and even stroke are reported in as many as 30% of cases and can persist even after the infection is over (so-called ‘long COVID’). These neurological symptoms are thought to be caused by brain inflammation, caused by the virus infecting the central nervous system of COVID-19 patients, however we still don’t understand the molecular mechanisms that trigger these symptoms. The neurological effects of COVID-19 share many similarities to neurodegenerative diseases such as Alzheimer’s and Parkinson’s in which the presence of cytotoxic protein-based amyloid aggregates is a common etiological feature. Following the hypothesis that some neurological symptoms of COVID-19 may also follow an amyloid etiology we performed a bioinformatic scan of the SARS-CoV-2 proteome, detecting peptide fr...
Advanced Science, 2020
Nanomechanical properties of amyloid fibrils and nanocrystals depend on their secondary and quate... more Nanomechanical properties of amyloid fibrils and nanocrystals depend on their secondary and quaternary structure, and the geometry of intermolecular hydrogen bonds. Advanced imaging methods based on atomic force microscopy (AFM) have unravelled the morphological and mechanical heterogeneity of amyloids, however a full understanding has been hampered by the limited resolution of conventional spectroscopic methods. Here, it is shown that single molecule nanomechanical mapping and infrared nanospectroscopy (AFM‐IR) in combination with atomistic modelling enable unravelling at the single aggregate scale of the morphological, nanomechanical, chemical, and structural transition from amyloid fibrils to amyloid microcrystals in the hexapeptides, ILQINS, IFQINS, and TFQINS. Different morphologies have different Young's moduli, within 2–6 GPa, with amyloid fibrils exhibiting lower Young's moduli compared to amyloid microcrystals. The origins of this stiffening are unravelled and relat...
Biophysical Journal, 2020
The Journal of Chemical Physics, 2020
Mixed solvents (i.e., binary or higher order mixtures of ionic or nonionic liquids) play crucial ... more Mixed solvents (i.e., binary or higher order mixtures of ionic or nonionic liquids) play crucial roles in chemical syntheses, separations, and electrochemical devices because they can be tuned for specific reactions and applications. Apart from fully explicit solvation treatments that can be difficult to parameterize or computationally expensive, there is currently no well-established first-principles regimen for reliably modeling atomic-scale chemistry in mixed solvent environments. We offer our perspective on how this process could be achieved in the near future as mixed solvent systems become more explored using theoretical and computational chemistry. We first outline what makes mixed solvent systems far more complex compared to single-component solvents. An overview of current and promising techniques for modeling mixed solvent environments is provided. We focus on so-called hybrid solvation treatments such as the conductor-like screening model for real solvents and the referen...
Scientific Reports, 2019
By combining atomistic and higher-level modelling with solution X-ray diffraction we analyse self... more By combining atomistic and higher-level modelling with solution X-ray diffraction we analyse self-assembly pathways for the IFQINS hexapeptide, a bio-relevant amyloid former derived from human lysozyme. We verify that (at least) two metastable polymorphic structures exist for this system which are substantially different at the atomistic scale, and compare the conditions under which they are kinetically accessible. We further examine the higher-level polymorphism for these systems at the nanometre to micrometre scales, which is manifested in kinetic differences and in shape differences between structures instead of or as well as differences in the small-scale contact topology. Any future design of structure based inhibitors of the IFQINS steric zipper, or of close homologues such as TFQINS which are likely to have similar structures, should take account of this polymorphic assembly.
Quarterly Reviews of Biophysics, 2017
Using atomistic simulations, we show the formation of stable triplet structure when particular GC... more Using atomistic simulations, we show the formation of stable triplet structure when particular GC-rich DNA duplexes are extended in solution over a timescale of hundreds of nanoseconds, in the presence of organic salt. We present planar-stacked triplet disproportionated DNA (Σ DNA) as a possible solution phase of the double helix under tension, subject to sequence and the presence of stabilising co-factors. Considering the partitioning of the duplexes into triplets of base pairs as the first step of operation of recombinase enzymes like RecA, we emphasise the structure–function relationship in Σ DNA. We supplement atomistic calculations with thermodynamic arguments to show that codons for ‘phase 1’ amino acids (those appearing early in evolution) are more likely than a lower entropy GC-rich sequence to form triplets under tension. We further observe that the four amino acids supposed (in the ‘GADV world’ hypothesis) to constitute the minimal set to produce functional globular protei...
Nature communications, Dec 20, 2017
The original version of this article contained an error in Fig. 5c. The label for the back series... more The original version of this article contained an error in Fig. 5c. The label for the back series of columns was incorrectly given as '1.5 mM pH 2', rather than the correct '1.5 mM pH 7'. This has now been corrected in both the PDF and HTML versions of the article.
Nature communications, Nov 7, 2017
Amyloidogenic model peptides are invaluable for investigating assembly mechanisms in disease rela... more Amyloidogenic model peptides are invaluable for investigating assembly mechanisms in disease related amyloids and in protein folding. During aggregation, such peptides can undergo bifurcation leading to fibrils or crystals, however the mechanisms of fibril-to-crystal conversion are unclear. We navigate herein the energy landscape of amyloidogenic peptides by studying a homologous series of hexapeptides found in animal, human and disease related proteins. We observe fibril-to-crystal conversion occurring within single aggregates via untwisting of twisted ribbon fibrils possessing saddle-like curvature and cross-sectional aspect ratios approaching unity. Changing sequence, pH or concentration shifts the growth towards larger aspect ratio species assembling into stable helical ribbons possessing mean-curvature. By comparing atomistic calculations of desolvation energies for association of peptides we parameterise a kinetic model, providing a physical explanation of fibril-to-crystal in...
The Journal of chemical physics, Jan 7, 2016
We investigate the early part of the crystal nucleation process in the hard sphere fluid using da... more We investigate the early part of the crystal nucleation process in the hard sphere fluid using data produced by computer simulation. We find that hexagonal order manifests continuously in the overcompressed liquid, beginning approximately one diffusion time before the appearance of the first "solid-like" particle of the nucleating cluster, and that a collective influx of particles towards the nucleation site occurs simultaneously to the ordering process: the density increases leading to nucleation are generated by the same individual particle displacements as the increases in order. We rule out the presence of qualitative differences in the early nucleation process between medium and low overcompressions and also provide evidence against any separation of translational and orientational order on the relevant lengthscales.
On the importance of density fluctuations to the process of crystal nucleation from the hard sphere fluid
We discuss the crystal nucleation pathway of a suspension of monodisperse hard spheres focusing o... more We discuss the crystal nucleation pathway of a suspension of monodisperse hard spheres focusing on the importance of density fluctuations prior to the nucleation event. We contrast time series of density fluctuations at different wavelengths with time series of the commonly considered structural order parameter, which is the size of the largest cluster of adjacent particles having significant hexagonal bond order measured using the method of q6q6 spherical harmonic products. We find that significant density fluctuations take place prior to the structural rearrangements, and suggest that these early drivers of nucleation have previously been overlooked as they are suppressed or relaxed by the structural rearrangements accompanying the formation of the nascent nucleus. The ensemble of nucleating trajectories studied was generated using forward flux sampling at low supersaturation.
Crystal nucleation mechanism in melts of short polymer chains under quiescent conditions and under shear flow
The Journal of chemical physics, Jan 28, 2014
We present a molecular dynamics simulation study of crystal nucleation from undercooled melts of ... more We present a molecular dynamics simulation study of crystal nucleation from undercooled melts of n-alkanes, and we identify the molecular mechanism of homogeneous crystal nucleation under quiescent conditions and under shear flow. We compare results for n-eicosane (C20) and n-pentacontahectane (C150), i.e., one system below the entanglement length and one above, at 20%-30% undercooling. Under quiescent conditions, we observe that entanglement does not have an effect on the nucleation mechanism. For both chain lengths, the chains first align and then straighten locally, then the local density increases and finally positional ordering sets in. At low shear rates the nucleation mechanism is the same as under quiescent conditions, while at high shear rates the chains align and straighten at the same time. We report on the effects of shear rate and temperature on the nucleation rates and estimate the critical shear rates, beyond which the nucleation rates increase with the shear rate. In...
Journal of Chemical Theory and Computation, 2013
Prediction of Twist of Amyloid Fibrils Using Molecular Dynamics
Many proteins and peptides form amyloid fibrils. These long, helically symmetric aggregates can b... more Many proteins and peptides form amyloid fibrils. These long, helically symmetric aggregates can be highly ordered but are not normally amenable to structure determination by X-ray crys- tallography or solution NMR. Therefore although amyloid fib rils of the same sequence can dis- play substantial variation in gross morphological feature s such as twist (depending on seeding and on growth conditions
Uploads
Papers by Joshua Berryman