Hydrogen properties and charges in a sub-1.2 Å resolution cryo-EM structure revealed by a cold field emission beam

The cold field emission (CFE) beam produces the less-attenuated contrast transfer function of electron microscopy, thereby enhancing high-resolution signals and this particularly benefits higher-resolution single particle cryogenic electron microscopy. Here, we present a sub-1.2 Å resolution structure of a standard protein sample, apoferritin. Image data were collected with the CFE beam in a high-throughput scheme while minimizing beam tilt deviations from the coma-free axis. A difference map reveals positive densities for most hydrogen atoms in the core region of the protein complex including those in water molecules, while negative densities around acidic amino-acid side chains likely represent negative charges. The position of the hydrogen densities depends on parent bonded-atom type, which is validated by an estimated level of coordinate errors.

Artificial Neurons Based on Ag/V2C/W Threshold Switching Memristors

Artificial synapses and neurons are two critical, fundamental bricks for constructing hardware neural networks. Owing to its high-density integration, outstanding nonlinearity, and modulated plasticity, memristors have attracted emerging attention on emulating biological synapses and neurons. However, fabricating a low-power and robust memristor-based artificial neuron without extra electrical components is still a challenge for brain-inspired systems. In this work, we demonstrate a single two-dimensional (2D) MXene(V2C)-based threshold switching (TS) memristor to emulate a leaky integrate-and-fire (LIF) neuron without auxiliary circuits, originating from the Ag diffusion-based filamentary mechanism. Moreover, our V2C-based artificial neurons faithfully achieve multiple neural functions including leaky integration, threshold-driven fire, self-relaxation, and linear strength-modulated spike frequency characteristics. This work demonstrates that three-atom-type MXene (e.g., V2C) memristors may provide an efficient method to construct the hardware neuromorphic computing systems.

DeepDISE: DNA Binding Site Prediction Using a Deep Learning Method

It is essential for future research to develop a new, reliable prediction method of DNA binding sites because DNA binding sites on DNA-binding proteins provide critical clues about protein function and drug discovery. However, the current prediction methods of DNA binding sites have relatively poor accuracy. Using 3D coordinates and the atom-type of surface protein atom as the input, we trained and tested a deep learning model to predict how likely a voxel on the protein surface is to be a DNA-binding site. Based on three different evaluation datasets, the results show that our model not only outperforms several previous methods on two commonly used datasets, but also demonstrates its robust performance to be consistent among the three datasets. The visualized prediction outcomes show that the binding sites are also mostly located in correct regions. We successfully built a deep learning model to predict the DNA binding sites on target proteins. It demonstrates that 3D protein structures plus atom-type information on protein surfaces can be used to predict the potential binding sites on a protein. This approach should be further extended to develop the binding sites of other important biological molecules.

Enhancing Carbon Acid pKa Prediction by Augmentation of Sparse Experimental Datasets with Accurate AIBL (QM) Derived Values

The prediction of the aqueous pKa of carbon acids by Quantitative Structure Property Relationship or cheminformatics-based methods is a rather arduous problem. Primarily, there are insufficient high-quality experimental data points measured in homogeneous conditions to allow for a good global model to be generated. In our computationally efficient pKa prediction method, we generate an atom-type feature vector, called a distance spectrum, from the assigned ionisation atom, and learn coefficients for those atom-types that show the impact each atom-type has on the pKa of the ionisable centre. In the current work, we augment our dataset with pKa values from a series of high performing local models derived from the Ab Initio Bond Lengths method (AIBL). We find that, in distilling the knowledge available from multiple models into one general model, the prediction error for an external test set is reduced compared to that using literature experimental data alone.

A Geometric Definition of Short to Medium Range Hydrogen-Mediated Interactions in Proteins

We present a method to rapidly identify hydrogen-mediated interactions in proteins (e.g., hydrogen bonds, hydrogen bonds, water-mediated hydrogen bonds, salt bridges, and aromatic π-hydrogen interactions) through heavy atom geometry alone, that is, without needing to explicitly determine hydrogen atom positions using either experimental or theoretical methods. By including specific real (or virtual) partner atoms as defined by the atom type of both the donor and acceptor heavy atoms, a set of unique angles can be rapidly calculated. By comparing the distance between the donor and the acceptor and these unique angles to the statistical preferences observed in the Protein Data Bank (PDB), we were able to identify a set of conserved geometries (15 for donor atoms and 7 for acceptor atoms) for hydrogen-mediated interactions in proteins. This set of identified interactions includes every polar atom type present in the Protein Data Bank except OE1 (glutamate/glutamine sidechain) and a clear geometric preference for the methionine sulfur atom (SD) to act as a hydrogen bond acceptor. This method could be readily applied to protein design efforts.

Atomic partial charge predictions for furanoses by random forest regression with atom type symmetry function

Atom type symmetry function that utilizes atom types defined in traditional force fields demonstrated improvements for describing structures of furanoses, and the capability of predicting their conformational adaptive charges with random forest regression models.