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

Designing an information system for updating land records in Bangladesh: action design ethnographic research (ADER)

Open Access. This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.This article has been made available through the Brunel Open Access Publishing Fund.Information Systems (IS) has developed through adapting, generating and applying diverse methodologies, methods, and techniques from reference disciplines. Further, Action Design Research (ADR) has recently developed as a broad research method that focuses on designing and redesigning IT and IS in organizational contexts. This paper reflects on applying ADR in a complex organizational context in a developing country. It shows that ADR requires additional lens for designing IS in such a complex organizational context. Through conducting ADR, it is seen that an ethnographic framework has potential complementarities for understanding complex contexts thereby enhancing the ADR processes. This paper argues that conducting ADR with an ethnographic approach enhances design of IS and organizational contexts. Finally, this paper aims presents a broader methodological framework, Action Design Ethnographic Research (ADER), for designing artefacts as well as IS. This is illustrated through the case of a land records updating service in Bangladesh

Heavy metal concentrations in sediments of streams affected by a sanitary landfill: A comparison of metal enrichment in two size sediment fractions

The purpose of this study was to determine if metal concentrations are enriched in two size sediment fractions of streams that receive landfill effluent and, if so, whether there is a greater extent of metal enrichment in one of the fractions. Sediment samples were collected from three streams adjacent to a sanitary landfill. Sediments representing control for the study were also collected from a stream not influenced by the landfill. All samples were sieved and the \u3c0.0625-mm and \u3c0.25-mm to \u3e0.149-mm size fractions from each sample were used in this study. The concentrations of acid-extractable Cu, Zn, Pb, and Cr for all samples were determined by atomic absorption techniques. Mean concentrations, coefficient of variation values, at test, and the variation of metal concentrations along the stream were used to analyze the data. Results indicated that Cu, Zn, Pb, and Cr concentrations were enriched in both size sediment fractions from the stream whose channel originated at the base of the landfill. Copper, Zn, and Pb concentrations were enriched in the \u3c0.0625-mm size sediments of the stream whose channel did not intersect the landfill. Copper, Zn, Pb, and Cr concentrations appear enriched in both size sediment fractions of the third stream, which formed from the confluence of the other two streams. The extent of metal enrichment was greater in the \u3c0.0625-mm size sediments. A decreasing trend of metal concentrations in a downstream direction was not present in the enriched sediments. This was true for each metal in both size sediment fractions