Multiple Parameter Replica Exchange Gaussian Accelerated Molecular Dynamics for Enhanced Sampling and Free Energy Calculation of Biomolecular Systems.

This study introduces a novel method named multiple parameter replica exchange Gaussian accelerated molecular dynamics (MP-Rex-GaMD), building on the Gaussian accelerated molecular dynamics (GaMD) algorithm. GaMD enhances sampling and retrieves free energy information for biomolecular systems by adding a harmonic boost potential to smooth the potential energy surface without the need for predefined reaction coordinates. Our innovative approach advances the acceleration power and energetic reweighting accuracy of GaMD by incorporating a replica exchange algorithm that enables the exchange of multiple parameters, including the GaMD boost parameters of force constant and energy threshold, as well as temperature. Applying MP-Rex-GaMD to the three model systems of dialanine, chignolin, and HIV protease, we demonstrate its superior capability over conventional molecular dynamics and GaMD simulations in exploring protein conformations and effectively navigating various biomolecular states across energy barriers. MP-Rex-GaMD allows users to accurately map free energy landscapes through energetic reweighting, capturing the ensemble of biomolecular states from low-energy conformations to rare high-energy transitions within practical computational time scales.

Utilizing Industrial Sludge Ash in Brick Manufacturing and Quality Improvement.

This research demonstrates changes in the behaviors and characteristics of sintered bricks while using industrial sludge ash (ISA) and waste glass (WG) as a replacement for clay in the brick manufacturing procedure. Owing to the limited amount of available land in Taiwan, it is becoming increasingly difficult to locate suitable sites for sanitary landfills, which is a common final disposal method for ash that is produced during thermal treatment in sludge factories. To meet the urgent need for land, the final waste disposal must convert this waste into a new resource. This research investigated the feasibility of using general industrial sludge ash waste, due to its abundance and high potential as a raw material in producing bricks. The result of this study shows that the bricks made from ISA and WG under a certain mixture proportion (ISA50%/WG40%/Clay10%) had excellent industrial potentials, such as compressive strength and water absorption rate. However, owing to the wide variety of components from different sources of ISA, the mixture proportion might vary accordingly. This study also analyzed the incineration index, proportion design, and process improvement, as well as investigating the possibility of increasing the total use of sludge ash as a resource. This study shows the potentials of utilizing wastes as raw materials in industrial manufacturing procedures. Therefore, more wastes can be tested and turned into resources in the future.

Mechanistic insights into ligand dissociation from the SARS-CoV-2 spike glycoprotein.

The COVID-19 pandemic, driven by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spurred an urgent need for effective therapeutic interventions. The spike glycoprotein of the SARS-CoV-2 is crucial for infiltrating host cells, rendering it a key candidate for drug development. By interacting with the human angiotensin-converting enzyme 2 (ACE2) receptor, the spike initiates the infection of SARS-CoV-2. Linoleate is known to bind the spike glycoprotein, subsequently reducing its interaction with ACE2. However, the detailed mechanisms underlying the protein-ligand interaction remain unclear. In this study, we characterized the pathways of ligand dissociation and the conformational changes associated with the spike glycoprotein by using ligand Gaussian accelerated molecular dynamics (LiGaMD). Our simulations resulted in eight complete ligand dissociation trajectories, unveiling two distinct ligand unbinding pathways. The preference between these two pathways depends on the gate distance between two α-helices in the receptor binding domain (RBD) and the position of the N-linked glycan at N343. Our study also highlights the essential contributions of K417, N121 glycan, and N165 glycan in ligand unbinding, which are equally crucial in enhancing spike-ACE2 binding. We suggest that the presence of the ligand influences the motions of these residues and glycans, consequently reducing accessibility for spike-ACE2 binding. These findings enhance our understanding of ligand dissociation from the spike glycoprotein and offer significant implications for drug design strategies in the battle against COVID-19.

Exploring additives beyond phthalates: Release from plastic mulching films, biodegradation and occurrence in agricultural soils.

It is widely recognized that applications of plastic films result in plastic pollution in agroecosystems. However, there is limited knowledge on the release and occurrence of additives beyond phthalates in agricultural soil. In this study, the rates of release and biodegradation of various additives, including phthalates, bisphenols, organophosphate esters, phenolic antioxidants, and ultraviolet absorbents from mulching films in soil were quantified by laboratory incubation. The rates of release and biodegradation ranged from 0.069 d-1 to 5.893 d-1 and from 1.43 × 10-3 d-1 to 0.600 d-1, respectively. Both of these rates were affected by temperature, flooding, and the properties of additives, films, and soils. An estimated 4000 metric tons of these additives were released into soil annually in China exclusively. The total concentrations of these additives in 80 agricultural soils varied between 228 and 3455 µg kg-1, with phenolic antioxidants, phthalates, and bisphenols accounting for 54.1%, 25.2%, and 17.9% of the total concentrations, respectively. A preliminary risk assessment suggested that the current levels of these additives could potentially present moderate hazards to the soil ecosystem.