Scalable Analysis of Dipole Moment Fluctuations for Characterizing Intermolecular Interactions and Structural Stability.

Accurately predicting protein-ligand interactions is essential in computational molecular biochemistry and in silico drug development. Monitoring changes in molecular dipole moments through molecular dynamics simulations provides valuable insights into dipole-dipole interactions, which are critical for understanding protein structure stability and predicting protein-ligand binding affinity. In this study, we propose a novel method to monitor changes in the interangle between dipole vectors of residue molecules within proteins and ligand molecules, aiming to evaluate the strength and consistency of interactions within the complex. Additionally, we extend the concept of positional root-mean-square fluctuation (RMSF), commonly used for protein structure stability analysis, to dipole moments, thus defining dipole moment RMSF. This enables us to analyze the stability of dipole moments for each residue within the protein and compare them across residues and between binding and non-binding complexes. Using the CRBP1-retinoic acid complex as our model system, we observed a significant difference in the interangle change of dipole moments for the key residue at the residue-level between the non-binding and binding complexes. Furthermore, we found that the dipole moment RMSF value of the non-binding complex was substantially larger than that of the binding complex, indicating greater dipole moment instability in the non-binding complex. Leveraging the concept of scalability inherent in the calculation of dipole moment vectors, we systematically expanded the residues within the protein's primary secondary structure. Our dipole moment analysis approach can provide valuable predictive insights into complex candidates, especially in situations where experimental comparisons are challenging.

Comparative molecular dynamics study on the features of binding and non-binding modes of retinoic acid in cellular retinol-binding protein (I).

Retinoids play crucial roles in various biological processes by interacting with their carrier proteins such as cellular retinol-binding protein (CRBP). Understanding the molecular interactions between retinoids and CRBP enables their pharmacological and biomedical applications. Experimentally, CRBP(I) does not bind to retinoic acid, but when arginine is introduced into 108th residue instead of glutamine (Q108R), it binds to retinoic acid. Here, molecular dynamics simulations were performed to understand the differences in the microscopic and dynamic behaviors of the non-binding wild-type CRBP(I)-retinoic acid and binding Q108R variant-retinoic acid complexes. The ligand RMSD and RMSF, the binding poses of binding motif amino acids, and the number of hydrogen bonds and salt-bridges revealed the relative instability of the non-binding complex. In particular, the ligand's terminal group showed very different dynamics and interactions. So far, most studies have focused on the binding characteristics of retinoids, but the features of their non-binding modes have not been studied well. This study provides some structural insights into the non-binding modes of a retinoid in CRBP, which may be applicable in retinoid-based drug discovery and protein engineering through computational modeling.

Printing Optimization of 3D Structure with Lard-like Texture Using a Beeswax-Based Oleogels.

In this study, we investigated the optimal conditions for 3D structure printing of alternative fats that have the textural properties of lard using beeswax (BW)-based oleogel by a statistical analysis. Products printed with over 15% BW oleogel at 50% and 75% infill level (IL) showed high printing accuracy with the lowest dimensional printing deviation for the designed model. The hardness, cohesion, and adhesion of printed samples were influenced by BW concentration and infill level. For multi-response optimization, fixed target values (hardness, adhesiveness, and cohesiveness) were applied with lard printed at 75% IL. The preparation parameters obtained as a result of multiple reaction prediction were 58.9% IL and 16.0% BW, and printing with this oleogel achieved fixed target values similar to those of lard. In conclusion, our study shows that 3D printing based on the BW oleogel system produces complex internal structures that allow adjustment of the textural properties of the printed samples, and BW oleogels could potentially serve as an excellent replacement for fat.

N-Acetylated Proline-Glycine-Proline Accelerates Cutaneous Wound Healing and Neovascularization by Human Endothelial Progenitor Cells.

Human endothelial progenitor cells (hEPCs) are promising therapeutic resources for wound repair through stimulating neovascularization. However, the hEPCs-based cell therapy has been hampered by poor engraftment of transplanted cells. In this study, we explored the effects of N-acetylated Proline-Glycine-Proline (Ac-PGP), a degradation product of collagen, on hEPC-mediated cutaneous wound healing and neovascularization. Treatment of hEPCs with Ac-PGP increased migration, proliferation, and tube-forming activity of hEPCs in vitro. Knockdown of CXCR2 expression in hEPCs abrogated the stimulatory effects of Ac-PGP on migration and tube formation. In a cutaneous wound healing model of rats and mice, topical application of Ac-PGP accelerated cutaneous wound healing with promotion of neovascularization. The positive effects of Ac-PGP on wound healing and neovascularization were blocked in CXCR2 knockout mice. In nude mice, the individual application of Ac-PGP treatment or hEPC injection accelerated wound healing by increasing neovascularization. Moreover, the combination of Ac-PGP treatment and hEPC injection further stimulated wound healing and neovascularization. Topical administration of Ac-PGP onto wound bed stimulated migration and engraftment of transplanted hEPCs into cutaneous dermal wounds. Therefore, these results suggest novel applications of Ac-PGP in promoting wound healing and augmenting the therapeutic efficacy of hEPCs.

Subsurface nanoimaging by broadband terahertz pulse near-field microscopy.

Combined with terahertz (THz) time-domain spectroscopy, THz near-field microscopy based on an atomic force microscope is a technique that, while challenging to implement, is invaluable for probing low-energy light-matter interactions of solid-state and biomolecular nanostructures, which are usually embedded in background media. Here, we experimentally demonstrate a broadband THz pulse near-field microscope that provides subsurface nanoimaging of a metallic grating embedded in a dielectric film. The THz near-field microscope can obtain broadband nanoimaging of the subsurface grating with a nearly frequency-independent lateral resolution of 90 nm, corresponding to ∼ λ/3300, at 1 THz, while the AFM only provides a flat surface topography.

Mechanistic insights into the C-H bond activation of hydrocarbons by chromium(IV) oxo and chromium(III) superoxo complexes.

The mechanism of the C-H bond activation of hydrocarbons by a nonheme chromium(IV) oxo complex bearing an N-methylated tetraazamacrocyclic cyclam (TMC) ligand, [Cr(IV)(O)(TMC)(Cl)](+) (2), has been investigated experimentally and theoretically. In experimental studies, reaction rates of 2 with substrates having weak C-H bonds were found to depend on the concentration and bond dissociation energies of the substrates. A large kinetic isotope effect value of 60 was determined in the oxidation of dihydroanthracene (DHA) and deuterated DHA by 2. These results led us to propose that the C-H bond activation reaction occurs via a H-atom abstraction mechanism, in which H-atom abstraction of substrates by 2 is the rate-determining step. In addition, formation of a chromium(III) hydroxo complex, [Cr(III)(OH)(TMC)(Cl)](+) (3), was observed as a decomposed product of 2 in the C-H bond activation reaction. The Cr(III)OH product was characterized unambiguously with various spectroscopic methods and X-ray crystallography. Density functional theory (DFT) calculations support the experimental observations that the C-H bond activation by 2 does not occur via the conventional H-atom-abstraction/oxygen-rebound mechanism and that 3 is the product formed in this C-H bond activation reaction. DFT calculations also propose that 2 may have some Cr(III)O(•-) character. The oxidizing power of 2 was then compared with that of a chromium(III) superoxo complex bearing the identical TMC ligand, [Cr(III)(O2)(TMC)(Cl)](+) (1), in the C-H bond activation reaction. By performing reactions of 1 and 2 with substrates under identical conditions, we were able to demonstrate that the reactivity of 2 is slightly greater than that of 1. DFT calculations again support this experimental observation, showing that the rate-limiting barrier for the reaction with 2 is slightly lower than that of 1.

Mononuclear manganese-peroxo and bis(µ-oxo)dimanganese complexes bearing a common N-methylated macrocyclic ligand.

Mononuclear Mn(III) -peroxo and dinuclear bis(µ-oxo)Mn(III) 2 complexes that bear a common macrocyclic ligand were synthesized by controlling the concentration of the starting Mn(II) complex in the reaction of H2 O2 (i.e., a Mn(III) -peroxo complex at a low concentration (≤1 mM) and a bis(µ-oxo)Mn(III) 2 complex at a high concentration (≥30 mM)). These intermediates were successfully characterized by various physicochemical methods such as UV-visible spectroscopy, ESI-MS, resonance Raman, and X-ray analysis. The structural and spectroscopic characterization combined with density functional theory (DFT) calculations demonstrated unambiguously that the peroxo ligand is bound in a side-on fashion in the Mn(III) -peroxo complex and the Mn2 O2 diamond core is in the bis(µ-oxo)Mn(III) 2 complex. The reactivity of these intermediates was investigated in electrophilic and nucleophilic reactions, in which only the Mn(III) -peroxo complex showed a nucleophilic reactivity in the deformylation of aldehydes.

Quantitative analysis of water distribution in human articular cartilage using terahertz time-domain spectroscopy.

The water distribution in human osteoarthritic articular cartilage has been quantitatively characterized using terahertz time-domain spectroscopy (THz TDS). We measured the refractive index and absorption coefficient of cartilage tissue in the THz frequency range. Based on our measurements, the estimated water content was observed to decrease with increasing depth cartilage tissue, showing good agreement with a previous report based on destructive biochemical methods.