Research articles

Transfer learning is known to enhance molecular property prediction in limited data sets, however, negative transfer due to insufficient relatedness between source and target tasks continues to be a major challenge. Here, the authors develop a principal gradient-based measurement to evaluate the quantitative transferability from the source property to the target property before applying transfer learning, significantly improving the transfer learning performance.

Understanding the stability and activity of freeze-dried bio-macromolecules at low degrees of hydration is crucial for pharmaceutical and food industries, however, the building of in silico models for dynamical studies at a molecular level needs careful consideration. Here, the authors propose a modelling protocol that mimics experimental protein lyophilization, and proteins in weakly hydrated amorphous states, and validate it against experimental neutron scattering data.

Identifying molecular properties of compounds that best correlate with outer membrane permeation and growth inhibition could guide the discovery of new antibiotics. Here, the authors evaluate 174 molecular descriptors in 1260 antimicrobial compounds and study their correlations with antibacterial activity in Gram-negative Pseudomonas aeruginosa to derive a statistical protocol to identify mechanistic predictors of outer membrane permeation.

Water at the surface of proteins is known to be critically important in maintaining their conformation and function, but the dynamics of the backbone hydration of peptides remains somewhat elusive. Here, the authors study the hydrogen-bonding structural dynamics of N-ethylpropionamide, a β-peptide model, in heavy water using nonlinear infrared spectroscopy and MD simulations.

Mass spectrometry-based quantitative chemoproteomics is widely used for the identification of protein targets as well as modified residues, however, sample preparation and data analysis remain tedious. Here, the authors develop silane-based cleavable linkers functionalized tandem mass tags as click-compatible isobaric tags, introducing the isobaric label earlier in sample preparation, achieving decreased sample preparation time, with high coverage and high-accuracy quantification.

Understanding the stability of the eye lens protein human gamma-D crystallin (HGD) is essential to developing tools to prevent the formation of cataracts, however, structural investigations of the response of HGD to ultraviolet radiation are lacking. Here, the authors use continuous illumination serial crystallography to directly probe the mechanism of R36S HGD in response to ultraviolet radiation damage.

Mass transport at surfaces determines the kinetics of processes such as heterogeneous catalysis and thin-film growth, but our fundamental understanding of the contributions of molecular degrees of freedom to the process remains incomplete. Here, the authors use neutron spectroscopy together with theoretical methods to explain the “rolling” motion of triphenylphosphine adsorbed on exfoliated graphite.

ATP phosphoribosyltransferase is a multi-protein complex where the catalytic protein HisGS is allosterically regulated by the regulatory protein HisZ; however, the protein dynamics of HisGS in enzyme catalysis remain underexplored. Here, the authors investigate the catalytic effect of isotope-labeled HisGS, revealing that the catalytic rate of HisZ-activated HisGS decreases in a mass-dependent fashion at low temperatures, which correlates to product release.

Reduced molecular graphs can integrate higher-level chemical information and leverage advantages from atom-level graph neural networks. Here, the authors introduce the Multiple Molecular Graph eXplainable model, investigating the effects of multiple molecular graphs, including Atom, Pharmacophore, JunctionTree, and FunctionalGroup, on model learning and interpretation from various perspectives

Individual metal atoms and few-atom metal clusters have shown promising catalytic activities, however, their exploitation in the total synthesis of complex organic molecules remains underexplored. Here, the authors develop a total synthesis of the bioactive natural product (±)-Licarin B involving key steps catalyzed by soluble individual Pd atoms and Cu/Pd/Pt clusters, achieving an 11-step linear synthesis and overall yield of 13.1%.

Wheat gluten is a bio-based alternative to fossil-based polymers in thermoplastic and crosslinked foams, and it has been shown that it is possible to extrude foams based on wheat gluten. Here, the authors explore the impact of three naturally occurring additives (genipin, gallic acid, and citric acid) on the mechanical and liquid absorption properties of foam-extruded wheat gluten.

Molecular editing has been used for the late-stage functionalization of chemical scaffolds at the atomic level, however, chemically editing carbohydrates by inserting a foreign glycan remains underexplored. Here, the authors develop a cut-insert-stitch editing reaction sequence to insert various carbohydrates and activated hydroxyacids into oligosaccharides.

Microbial natural products are an important source for antibiotic discovery, however, their efficient dereplication remains challenging. Here, the authors develop an analytical pipeline, nanoRAPIDS, to prioritize low abundance bioactive compounds at nanoscale, by integrating the bioassay of interest, automated mass spectrometry identification and GNPS-based dereplication, resulting in the discovery of saquayamycin N from Streptomyces sp. MBT84.

Heterogeneous catalysis that occurs when the anodic and cathodic reactions are short-circuited in an appropriate electrolyte is conceptualized as mixed-potential-driven catalysis, however, its theoretical framework remains underexplored. Here, the authors propose the overpotentials as the driving force of the catalysis and extend Prigogine’s theory to formulate the kinetic equations for the energy conversion from the cathodic and anodic half-reactions into overpotentials, by formation of a mixed potential determined by the catalytic activity.

Highly energetic charge carriers generated in plasmon-assisted electrocatalysis can increase reaction rates and impart novel selectivity trends, but a simple protocol to differentiate between thermal and nonthermal plasmonic contributions is lacking. Here, the authors use cyclic voltammetry and finite element simulations to show direct interband excitation of gold by visible light exclusively enhances current density via photothermal heating, while plasmon excitation leads to photothermal and nonthermal enhancements.

Cobalt-based materials have a wide range of applications from information storage to electromagnetic absorbers in aerospace manufacturing, but the corrosion of cobalt nanosurfaces is poorly explored. Here, the authors combine mass spectrometry and DFT to study gas-phase reactions of Co_n^±/0 (n = 1–30) with water and oxygen and find that only anionic cobalt clusters give rise to water dissociation, whereas the cationic and neutral ones are limited to water adsorption.

Bicyclic peptides exhibit improved metabolic stabilities, membrane permeabilities, and target specificities over their linear and mono-cyclic counterparts, however, efficient bicyclization remains challenging. Here, the authors develop a one-pot tandem chemoenzymatic bicyclization by combination of penicillin-binding protein-type thioesterase-mediated head-to-tail macrolactamization and copper(I)-catalyzed azide–alkyne cycloaddition.

Oxide-derived copper materials display high catalytic activities for the electrochemical reduction of carbon dioxide, but the mechanisms surrounding this high performance are not fully understood. Here, the authors use time-resolved operando spectroscopy to probe the structural dynamics of copper oxide reduction and reformation, both in the bulk and on the surface of copper foam catalysts.

Norcoclaurine synthase from Thalictrum flavum (TfNCS) has been demonstrated to display high stereospecificity and yield in catalyzing the Pictet-Spengler reaction of dopamine with chiral aldehydes, however, the mechanism and factors related to this high stereospecificity remain unclear. Here, the authors conduct quantum chemical calculations and reveal the rate-limiting step and differential energy barriers for the reactions of two enantiomers of α-methylphenylacetaldehyde, as well as key residues related to stereospecificity.

Polyethylene terephthalate (PET) can be depolymerized by the Ideonella sakaiensis PETase enzyme, however, questions remain about the precise catalytic mechanism. Here, the authors use unbiased QM/MM MD simulations to determine optimal mechanistic descriptions of the acylation and deacylation reactions, revealing the rate-limiting step and key interactions within the catalytic triad and Trp185 conformation.