The time step of atomistic molecular dynamics (MD) simulations is determined by the fastest motions in the system and is typically limited to 2 fs. An increasingly popular approach is to increase the mass of the hydrogen atoms to ∼3 amu and decrease the mass of the parent atom by an equivalent amount. This approach, known as hydrogen-mass repartitioning (HMR), permits time steps up to 4 fs with reasonable simulation stability. While HMR has been applied in many published studies to date, it has not been extensively tested for membrane-containing systems. Here, we compare the results of simulations of a variety of membranes and membrane–protein systems run using a 2 fs time step and a 4 fs time step with HMR. For pure membrane systems, we find almost no difference in structural properties, such as area-per-lipid, electron density profiles, and order parameters, although there are differences in kinetic properties such as the diffusion constant. Conductance through a porin in an applied field, partitioning of a small peptide, hydrogen-bond dynamics, and membrane mixing show very little dependence on HMR and the time step. We also tested a 9 Å cutoff as compared to the standard CHARMM cutoff of 12 Å, finding significant deviations in many properties tested. We conclude that HMR is a valid approach for membrane systems, but a 9 Å cutoff is not.

The management of chronic wounds in the elderly such as pressure injury (also known as bedsore or pressure ulcer) is increasingly important in an ageing population. Accurate classification of the stage of pressure injury is important for wound care planning. Nonetheless, the expertise required for staging is often not available in a residential care home setting. Artificial-intelligence (AI)-based computer vision techniques have opened up opportunities to harness the inbuilt camera in modern smartphones to support pressure injury staging by nursing home carers. In this paper, we summarise the recent development of smartphone or tablet-based applications for wound assessment. Furthermore, we present a new smartphone application (app) to perform real-time detection and staging classification of pressure injury wounds using a deep learning-based object detection system, YOLOv4. Based on our validation set of 144 photos, our app obtained an overall prediction accuracy of 63.2%. The per-class prediction specificity is generally high (85.1%–100%), but have variable sensitivity: 73.3% (stage 1 vs. others), 37% (stage 2 vs. others), 76.7 (stage 3 vs. others), 70% (stage 4 vs. others), and 55.6% (unstageable vs. others). Using another independent test set, 8 out of 10 images were predicted correctly by the YOLOv4 model. When deployed in a real-life setting with two different ambient brightness levels with three different Android phone models, the prediction accuracy of the 10 test images ranges from 80 to 90%, which highlight the importance of evaluation of mobile health (mHealth) application in a simulated real-life setting. This study details the development and evaluation process and demonstrates the feasibility of applying such a real-time staging app in wound care management.

exchange, ReMDFF, provide a precise tool to fit atomic structures of a protein inside an electron density map to improve the resolution of the protein structure. Typically, MDFF incorporates the electron microscopy (EM) data as an external potential (U EM ) added to the standard molecular dynamics force field, such that the high-density areas in the map correspond to energy minima, where the atoms are subject to forces proportional to the gradient of the EM map. However, the error involved in biasing the standard potential with U EM has not been explored yet. Re-casting U EM in an integro-differential form, reveals a hidden error energy term reminiscent of long-range interactions between stationary masses. This additional contribution to the force filed unnecessarily contorts the molecular geometries during an MDFF refinement. We perform, a quantitative assessment of the effect of this hidden error term in MDFF's grid force field using recently published structures using EM to Protein Data Bank, of varying residues, 200 -20,000 with 3-8 Å resolution and their corresponding electron density maps. The initial systems are prepared using default MDFF settings, for different grid force scaling parameter. The protein structure files are modified by replacing the charge with atoms mass multiplied by a factor proportional to the error term. The mass-based coulomb like potential is then calculated using NAMD Energy where the structures corresponding to low and high error term values are used and run through MolProbity for comparison of their relative stabilities. Our results indicate, re-weighting an ensemble of structures based on the error-energy term, provides improvement in determining both stereochemical and thermodynamic correct structures of proteins from electron density maps. . The enormous improvements in computational power in recent years means that we can routinely runs simulations of biologically interesting systems out to the microsecond scale or longer. However, in many cases their scientific impact is limited by an inability to extract useful information from this wealth of data. We created LOOS to unlock this previously unrealized potential. Molecular dynamics is unique among biophysical techniques in that the raw data can be interrogated in a multitude of ways; getting the most out of the data usually requires exploration and iterative refinement. LOOS is designed to make this process easy and efficient, to minimize the friction between a user and her data. LOOS can be viewed in two ways: 1) It is a suite of well-validated, easy-to-use tools for analyzing molecular dynamics simulations. These tools include common tasks, such as trajectory manipulation, as well as more advanced techniques such as analysis of simulation convergence, 3D histograms, and Voronoi decomposition, with a particular focus on membranes and membrane-bound proteins. 2) It is a tool for making tools. At its heart, LOOS is a Cþþ library covered with a Python interface, for the optimal mix of high performance and ease of development. L...

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