Biophysica, Volume 1, Issue 3 (September 2021) – 7 articles

A dataset containing the experimental values of the equilibrium binding constants of clinical drugs, and some other organic ligands with human and mammalian (predominantly bovine) serum albumins, is assembled. The affinity of drugs to albumin governs their pharmacokinetic properties, related to permeability through physiological barriers and distribution within the organism. The dataset contains 1755 records gathered from 346 original literature sources describing the albumin affinity of 324 different substances. The data were extracted from both articles and existing protein-binding databases applied strict data selection rules in order to exclude the values influenced by the third-party compounds. The dataset provides the details on the experimental conditions of the measurements, such as temperature; protein and ligand concentrations; buffer pH, composition and concentration; and the method and model used for the binding constant calculations. Analysis of the data reveals discrepancies between the values from different studies, as well as the significant influence of the measurement method. Averaging the values from multiple independent measurements from the dataset may help to determine the reliable values of the binding constants. The dataset can be used as the reference dataset for the development of predictive models to calculate binding constants, and as the choice for the experimental setup in the future albumin-binding studies. Full article

The chemical step of Shikimate Kinase Helicobacter pylori, involving the transfer of a phosphoryl group, has been studied by using quantum mechanical and molecular mechanical (QM/MM) methods. Understanding the mechanism of this chemical step, present in bacteria and other microorganisms but absent in humans, can lead to the development of novel drugs for the treatment of common diseases caused by those pathogenic organisms. Different mechanisms including associative, dissociative, and concerted have been proposed up to now but there is not a consensus on the type of pathway that the reaction follows. Herein, we found that the mechanism has features from the associative and concerted types. An analysis of the free energy landscape of the chemical step reveals that the reaction is a two-step process without a well-defined intermediate state. Full article

The concentration detection limit (DL) of biomacromolecules attainable using a nanowire detector has become a topical issue. A DL of 10⁻¹⁵ M is required to reveal oncological and infectious diseases at an early stage. This study discusses the DL experimentally attainable in the subfemtomolar concentration range, and possible mechanisms explaining such a low-concentration DL through the cooperative effect of biomacromolecular complexes formed on the surface of the nanowire (NW) chip near the nanowire. Full article

In 2019, novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began infecting humans, resulting in the COVID-19 pandemic. While the push for development of vaccines has yielded some positive results, the emergence of additional variants has led to concerns surrounding sustained vaccine effectiveness as the variants become the dominant strains. This work was undertaken to develop peptide-based antivirals capable of targeting both the wildtype (WT) heptad repeat 1 (HR1) domain of SARS-CoV-2 and the new HR1 variants which have developed. In silico protein mutagenesis, structural characterization, and protein–protein molecular docking were utilized to determine molecular interactions which facilitated binding of peptide-based antivirals targeting the HR1 domains. Molecular dynamics simulations were utilized to predict the final binding affinities of the top five peptide inhibitors designed. This work demonstrated the importance of hydrophobic interactions in the hydrophobic gorge and in the rim of the HR1 domain. Additionally, the placement of charged residues was shown to be essential in maximizing electrostatic interactions. The top five designed peptide inhibitors were all demonstrated to maintain good binding affinity to the WT and the variant HR1 SARS-CoV-2 domains. Therefore, the peptide inhibitors designed in this work could serve as potent antivirals which are effective in targeting both the original SARS-CoV-2 and the HR1 variants that have developed. Full article

Infection can hinder the process of wound healing, so it is important to begin antibacterial treatment quickly after a wound forms. Plasma activated water (PAW) can inactivate a variety of common wound infection bacteria. In this study, we compared the effects of PAW prepared with portable surface discharge plasma equipment and medical alcohol on wound healing in a mouse full-thickness skin wound model. The effectiveness of wound healing processes in mice was ranked accordingly: PAW treatment group > medical alcohol treatment group > control group. In order to further understand the mechanism of PAW in promoting wound healing, we tested the expression levels of the pro-inflammatory factors interleukin (IL)-1β and IL-6, the anti-inflammatory factor IL-10, and vascular endothelial growth factor (VEGF). The results showed that PAW promoted the release of pro-inflammatory factors and anti-inflammatory factors from the wounds in mice, which allowed the mice in the treatment group to transition out of the inflammatory period early and enter the next stage of wound healing. The expression level of VEGF in the wounds of mice in the PAW treatment group was higher, which indicates that the microvessels around the wound in the PAW treatment group proliferated faster, and thus the wound healed faster. PAW biosafety experiments showed that PAW did not significantly affect the appearance, morphology, or tissue structure of internal organs, or blood biochemical indicators in mice. In general, PAW prepared via portable devices is expected to become more widely used given its convenience, affordability, and lack of side effects in promoting wound healing. Full article

Estimation of solvent entropy from equilibrium molecular dynamics simulations is a long-standing problem in statistical mechanics. In recent years, methods that estimate entropy using k-th nearest neighbours (kNN) have been applied to internal degrees of freedom in biomolecular simulations, and for the rigorous computation of positional-orientational entropy of one and two molecules. The mutual information expansion (MIE) and the maximum information spanning tree (MIST) methods were proposed and used to deal with a large number of non-independent degrees of freedom, providing estimates or bounds on the global entropy, thus complementing the kNN method. The application of the combination of such methods to solvent molecules appears problematic because of the indistinguishability of molecules and of their symmetric parts. All indistiguishable molecules span the same global conformational volume, making application of MIE and MIST methods difficult. Here, we address the problem of indistinguishability by relabeling water molecules in such a way that each water molecule spans only a local region throughout the simulation. Then, we work out approximations and show how to compute the single-molecule entropy for the system of relabeled molecules. The results suggest that relabeling water molecules is promising for computation of solvation entropy. Full article

In vitro and in vivo methods of Raman spectroscopy have been developed to assess the degree of mineralization of the enamel of different functional groups. This article presents comparative studies that were carried out using scanning Raman microspectroscopy with various sources of laser excitation with wavelengths of 532, 785, and 1064 nm. It is shown that the intensity of Raman scattering of enamel can be a measure of its thickness. The obtained dependence of the Raman scattering intensity on the distance from the incisal edge is in good agreement with the literature data, where two independent methods (computer tomography and electron microscopy) are used to determine the enamel thickness values. The proposed methods can be considered as potential quantitative methods for express diagnostics of the state of tooth enamel in vivo. Full article