Neuropilin-1 Protein May Serve as a Receptor for SARS-CoV-2 Infection: Evidence from Molecular Dynamics Simulations.

The binding of the virus to host cells is the first step in viral infection. Human cell angiotensin converting enzyme 2 (ACE2) is the most popular receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), while other receptors have recently been observed in experiments. Neuropilin-1 protein (NRP1) is one of them, but the mechanism of its binding to the wild type (WT) and different variants of the virus remain unclear at the atomic level.

SARS-CoV-2 Omicron Subvariants Do Not Differ Much in Binding Affinity to Human ACE2: A Molecular Dynamics Study.

The emergence of the variant of concern Omicron (B.1.1.

Theoretical insights into the HO-induced oxidation of chlorpyrifos pesticide: Mechanism, kinetics, ecotoxicity, and cholinesterase inhibition of degradants.

The oxidation of the common pesticide chlorpyrifos (CPF) initiated by HO radical and the risks of its degradation products were studied in the gaseous and aqueous phases via computational approaches. Oxidation mechanisms were investigated, including H-, Cl-, CH- abstraction, HO-addition, and single electron transfer. In both phases, HO-addition at the C of the pyridyl ring is the most energetically favorable and spontaneous reaction, followed by H-abstraction reactions at methylene groups (i.

Identifying inhibitors of NSP16-NSP10 of SARS-CoV-2 from large databases.

The COVID-19 pandemic, which has already claimed millions of lives, continues to pose a serious threat to human health, requiring the development of new effective drugs. Non-structural proteins of SARS-CoV-2 play an important role in viral replication and infection. Among them, NSP16 (non-structured protein 16) and its cofactor NSP10 (non-structured protein 10) perform C2'-O methylation at the 5' end of the viral RNA, which promotes efficient virus replication.

SARS-CoV-2 Omicron Variant Binds to Human Cells More Strongly than the Wild Type: Evidence from Molecular Dynamics Simulation.

The emergence of the variant of concern Omicron (B.1.1.

Amyloid β Dodecamer Disrupts the Neuronal Membrane More Strongly than the Mature Fibril: Understanding the Role of Oligomers in Neurotoxicity.

The amyloid cascade hypothesis states that senile plaques, composed of amyloid β (Aβ) fibrils, play a key role in Alzheimer's disease (AD). However, recent experiments have shown that Aβ oligomers are more toxic to neurons than highly ordered fibrils. The molecular mechanism underlying this observation remains largely unknown.

Determination of Multidirectional Pathways for Ligand Release from the Receptor: A New Approach Based on Differential Evolution.

Steered molecular dynamics (SMD) simulation is a powerful method in computer-aided drug design as it can be used to access the relative binding affinity with high precision but with low computational cost. The success of SMD depends on the choice of the direction along which the ligand is pulled from the receptor-binding site. In most simulations, the unidirectional pathway was used, but in some cases, this choice resulted in the ligand colliding with the complex surface of the exit tunnel.

Elastic moduli of normal and cancer cell membranes revealed by molecular dynamics simulations.

Recent studies indicate that there are mechanical differences between normal cells and cancer cells. Because the cell membrane takes part in a variety of vital processes, we test the hypothesis of whether or not two fundamental alterations in the cell membrane, , the overexpression of phosphatidylserine lipids in the outer leaflet and a reduction in cholesterol concentration, could cause the softening in cancer cells. Adopting ten models of normal and cancer cell membranes, we carry out 1 μs all-atom molecular dynamics simulations to compare the structural properties and elasticity properties of two membrane types.

Biorenewable, transparent, and oxygen/moisture barrier nanocellulose/nanochitin-based coating on polypropylene for food packaging applications.

Aluminum-coated polypropylene films are commonly used in food packaging because aluminum is a great gas barrier. However, recycling these films is not economically feasible. In addition, their end-of-life incineration generates harmful alumina-based particulate matter.

Nanomechanical Stability of Aβ Tetramers and Fibril-like Structures: Molecular Dynamics Simulations.

Alzheimer's disease (AD) is a neurodegenerative disorder and one of the main causes of dementia. The disease is associated with amyloid beta (Aβ) peptide aggregation forming initial clusters and then fibril structure and plaques. Other neurodegenerative diseases such as type 2 diabetes, amyotrophic lateral sclerosis, and Parkinson's disease follow a similar mechanism.

Remdesivir Strongly Binds to Both RNA-Dependent RNA Polymerase and Main Protease of SARS-CoV-2: Evidence from Molecular Simulations.

The outbreak of a new coronavirus SARS-CoV-2 (severe acute respiratory syndrome-coronavirus 2) has caused a global COVID-19 (coronavirus disease 2019) pandemic, resulting in millions of infections and thousands of deaths around the world. There is currently no drug or vaccine for COVID-19, but it has been revealed that some commercially available drugs are promising, at least for treating symptoms. Among them, remdesivir, which can block the activity of RNA-dependent RNA polymerase (RdRp) in old SARS-CoV and MERS-CoV viruses, has been prescribed to COVID-19 patients in many countries.

Emergence of Barrel Motif in Amyloid-β Trimer: A Computational Study.

Amyloid-β (Aβ) peptides form assemblies that are pathological hallmarks of Alzheimer's disease. Aβ oligomers are soluble, mobile, and toxic forms of the peptide that act in the extracellular space before assembling into protofibrils and fibrils. Therefore, oligomers play an important role in the mechanism of Alzheimer's disease.

Does SARS-CoV-2 Bind to Human ACE2 More Strongly Than Does SARS-CoV?

The 2019 novel coronavirus (SARS-CoV-2) epidemic, which was first reported in December 2019 in Wuhan, China, was declared a pandemic by the World Health Organization in March 2020. Genetically, SARS-CoV-2 is closely related to SARS-CoV, which caused a global epidemic with 8096 confirmed cases in more than 25 countries from 2002 to 2003. Given the significant morbidity and mortality rate, the current pandemic poses a danger to all of humanity, prompting us to understand the activity of SARS-CoV-2 at the atomic level.

Investigation of Binding Affinity between Potential Antiviral Agents and PB2 Protein of Influenza A: Non-equilibrium Molecular Dynamics Simulation Approach.

The PB2 protein of the influenza virus RNA polymerase is a major virulence determinant of influenza viruses. It binds to the cap structure at the 5' end of host mRNA to generate short capped RNA fragments that are used as primers for viral transcription named cap-snatching. A large number of the compounds were shown to bind the minimal cap-binding domain of PB2 to inhibit the cap-snatching machinery.

Computational Model to Unravel the Function of Amyloid-β Peptides in Contact with a Phospholipid Membrane.

Divalent cations have a strong impact on the properties of phospholipid membranes, where amyloid-β peptides exert effects related to possible functional or pathological roles. In this work, we use an atomistic computational model of dimyristoyl-phosphatidylcholine (DMPC) membrane bilayers. We perturb this model with a simple model of divalent cations (Mg) and with a single amyloid-β (Aβ) peptide of 42 residues, both with and without a single Cu ion bound to the N-terminus.

Structure and Physicochemical Properties of the Aβ42 Tetramer: Multiscale Molecular Dynamics Simulations.

Despite years of intensive research, little is known about oligomeric structures present during Alzheimer's disease (AD). Excess of amyloid beta (Aβ) peptides and their aggregation are the basis of the amyloid cascade hypothesis, which attempts to explain the causes of AD. Because of the intrinsically disordered nature of Aβ monomers and the high aggregation rate of oligomers, their structures are almost impossible to resolve using experimental methods.

Erythromycin, Cethromycin and Solithromycin display similar binding affinities to the E. coli's ribosome: A molecular simulation study.

Macrolide antibiotics bind to the exit tunnel of the ribosome and inhibit protein synthesis blocking its translocation. Thus, antibiotics including the known macrolide Erythromycin (ERY) are active against bacteria. However, at present, some bacteria show resistance to drugs, which requires the development of new powerful antibacterial agents.

The Renewable and Sustainable Conversion of Chitin into a Chiral Nitrogen-Doped Carbon-Sheath Nanofiber for Enantioselective Adsorption.

Well-known hard-template methods for nitrogen (N)-doped chiral carbon nanomaterials require complicated construction and removal of the template, high-temperature pyrolysis, harsh chemical treatments, and additional N-doping processes. If naturally occurring chiral nematic chitin nanostructures [(C H NO ) ] in exoskeletons were wholly transformed into an N-doped carbon, this would be an efficient and sustainable method to obtain a useful chiral nanomaterial. Here, a simple, sacrificial-template-free, and environmentally mild method was developed to produce an N-doped chiral nematic carbon-sheath nanofibril hydrogel with a surface area >300 m  g and enantioselective properties from renewable chitin biomass.

Sustainable Boron Nitride Nanosheet-Reinforced Cellulose Nanofiber Composite Film with Oxygen Barrier without the Cost of Color and Cytotoxicity.

This paper introduces a boron nitride nanosheet (BNNS)-reinforced cellulose nanofiber (CNF) film as a sustainable oxygen barrier film that can potentially be applied in food packaging. Most commodity plastics are oxygen-permeable. CNF exhibits an ideal oxygen transmission rate (OTR) of <1 cc/m²/day in highly controlled conditions.

A ball milling-based one-step transformation of chitin biomass to organo-dispersible strong nanofibers passing highly time and energy consuming processes.

Chitin, a sustainable and functional biological macromolecule, can be converted into chitin nanofibers (ChNFs), and are applicable as a mechanically reinforcing and bioactive filler for polymer matrices. Improving the performance of ChNFs typically relies on their nanofibrilization and miscibility with matrices. To transform chitin biomass into organo-dispersible ChNFs, a series of time-/energy-consuming chemical and mechanical treatments are required: 1) deacetylation, 2) disintegration, 3) surface modification to minimize their aggregation through hydrogen bonds, 4) drying, and 5) re-dispersion.

Five different chitin nanomaterials from identical source with different advantageous functions and performances.

Chitin is a renewable and sustainable biomass material that can be converted into various one-dimensional crystalline nanomaterials different in 1) length, 2) diameter, 3) charge density, 4) type of charge, and 5) crystallinity via diverse top-down synthetic methods. These nanomaterials have great potential as sustainable reinforcing and biologically functional materials. The proper design of chitin nanomaterials maximizes their performances in specific applications.

Investigation of Binding Affinity Between Prokaryotic Proteins (AHU-IHF) and DNAs: Steered Molecular Dynamics Approach.

The aim of this work is to investigate the binding affinity between the prokaryotic proteins-AHU-IHF proteins (AHU (AHU2, TR3, and AHU6) and IHF (IHF-WT and IHF-βE44A))-and DNAs (DNA, H'-DNA, and H'44A-DNA) by using the steered molecular dynamics (SMD) simulation and the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) method. The gained results show that although the fluctuation of the pulling force yielded the change of the pulling work, the higher pulling work of the AHU/DNA complexes in comparison to those of the IHF/DNA complexes is not only dependent on the pulling force but also controlled by the change of the trajectory in SMD simulation process. In this study, the pulling work profile not only described the pulling pathway of the complexes but also reflected the hindered process of DNAs when AHU-IHF proteins come out from the binding pocket of DNAs.

Erythromycin leads to differential protein expression through differences in electrostatic and dispersion interactions with nascent proteins.

The antibiotic activity of erythromycin, which reversibly binds to a site within the bacterial ribosome exit tunnel, against many gram positive microorganisms indicates that it effectively inhibits the production of proteins. Similar to other macrolides, the activity of erythromycin is far from universal, as some peptides can bypass the macrolide-obstructed exit tunnel and become partially or fully synthesized. It is unclear why, at the molecular level, some proteins can be synthesized while others cannot.