Butyrylcholinesterase is a key enzyme that catalyzes the hydrolysis of the neurotransmitter acetylcholine and shows an increased activity in patients suffering from Alzheimer’s disease (AD), making this enzyme a primary target in treating AD. Central to this problem, and to similar scenarios involving biomolecular recognition, is our understanding of the nature of the protein-ligand complex. The butyrylcholinesterase enzyme was studied via all-atom, explicit solvent, ensemble molecular dynamics simulations sans inhibitor and in the presence of three dialkyl phenyl phosphate inhibitors of known potency to a cumulative sampling of over 40 μs. Following the relaxation of these ensembles to conformational equilibria, binding modes for each inhibitor were identified. While classical models, which assume significant reduction in protein and ligand conformational entropies, continue to be favored in contemporary studies, our observations contradict those assumptions: bound ligands occupy many conformational states, thereby stabilizing the complex, while also promoting protein flexibility.

Massive all-atom molecular dynamics simulations were conducted across a distributed computing network to study the folding, unfolding, misfolding and conformational plasticity of the high-efficiency frameshifting double mutant of the 26 nt potato leaf roll virus RNA pseudoknot. Our robust sampling, which included over 40 starting structures spanning the spectrum from the extended unfolded state to the native fold, yielded nearly 120 μs of cumulative sampling time. Conformational microstate transitions on the 1.0 ns to 10.0 μs timescales were observed, with post-equilibration sampling providing detailed representations of the conformational free energy landscape and the complex folding mechanism inherent to the pseudoknot motif. Herein, we identify and characterize two alternative native structures, three intermediate states, and numerous misfolded states, the latter of which have not previously been characterized via atomistic simulation techniques. While in line with previous thermodynamics-based models of a general RNA folding mechanism, our observations indicate that stem-strand-sequence-separation may serve as an alternative predictor of the order of stem formation during pseudoknot folding. Our results contradict a model of frameshifting based on structural rigidity and resistance to mechanical unfolding, and instead strongly support more recent studies in which conformational plasticity is identified as a determining factor in frameshifting efficiency.

The Krong No volcanic caves at the Dak Nong UNESCO Global Geopark (Dak Nong UGGp) were discovered in 2007. Between 2017 and the present, they were comprehensively studied and evaluated for heritage value from the perspectives of geology, biology and cultural studies. These primitive, endogenic caves are characterized by rich and diverse interior formations, representing seven types of geological heritage as classified by the UNESCO and its GILGES classification system. The applicable types are A (Paleontology), B (Geomorphology), C (Paleo-Environment), D (Rock), E (Stratigraphy), F (Minerals), and I (Tectonics). The cave system’s wildlife is highly diverse and includes a number of newly discovered species endemic to Krong No. Thanks to research and excavation work, many types of archaeological artifacts have been discovered in the Krong No volcanic caves, including relics of residence, a tool-making site, burial artifacts, a makeshift hunting camp, and some artifacts possibly expressive of religious ritual. All of these are unique, valuable and rare. The various types of heritage discovered in the Krong No volcanic caves constitute the premise of an on-site conservation museum, established to promote heritage of value, teaching and scholarship, as well as community education and recreation. This article introduces a new direction for further research, related to the development of an on-site conservation museum of the volcanic cave heritage in the context of sustainable socio-economic development.

Survey on invertebrate biodiversity of volcanic caves in Krong No, Dak Nong province, Vietnam was carried in 2018 and 2019. The survey were done in 8 typical caves are Co cave (475 m long), C1 cave (402 m), C2 cave (402 m), C3 cave (716 m), C4 cave (251 m), C6 cave (180 m), C6.1 cave (293 m) and C7 cave (1066 m). The survey result recorded 41 species, 31 families of 5 classes, 13 orders of invertebrate at volcanic caves in Krong No. It is expected that 13 species will become new taxa, for example a scorpion of the Chaerilidae family, Chaerilus chubluk Lourenco, Tran & Pham, 2020 in the Co cave. The large and long caves with a complicated structure with many corners are more valuable in term of biological diversity than the small caves with a simple structure.

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