Benchmarking ANI potentials as a rescoring function and screening FDA drugs for SARS-CoV-2 M.

Here, we introduce the use of ANI-ML potentials as a rescoring function in the host-guest interaction in molecular docking. Our results show that the "docking power" of ANI potentials can compete with the current scoring functions at the same level of computational cost. Benchmarking studies on CASF-2016 dataset showed that ANI is ranked in the top 5 scoring functions among the other 34 tested.

Computational analysis of substrate recognition of Sars-Cov-2 Mpro main protease.

M main protease takes an essential role in the Sars-Cov-2 viral life cycle by releasing the individual protein from the single poly-peptide chain via proteolytic cleavage in the beginning of the viral infection. Interfering with this step by inhibiting the protease with small compound-based inhibitors has been proven to be an effective strategy to treat the infection. Thus, understanding the substrate recognition mechanism of the M main protease has gained great interest from the beginning of the pandemic.

Exploring potential kinase inhibitors: a combined docking, MD and QSAR studies.

Malaria is a disease caused mostly by falciparum, affects millions of people each year. The kinases are validated targets for malaria infection. In this study, we investigate for real and hypothetical compounds that can inhibit cyclic guanosine monophosphate (CGMP)-dependent protein kinase using molecular docking combined similarity analysis, molecular dynamics simulations, quantitative structure activity relationship (QSAR).

Exploring epigenetic drugs as potential inhibitors of SARS-CoV-2 main protease: a docking and MD simulation study.

The COVID-19 pandemic has caused havoc around the globe since 2019 and is considered the largest global epidemic of the twentieth century. Although the first antiviral drug, Remdesivir, was initially introduced against COVID‑19, virtually no tangible therapeutic drugs exist to treat SARS-CoV-2 infection. FDA-approved Paxlovid (Nirmatrelvir supplemented by Ritonavir) was recently announced as a promising drug against the SARS-CoV-2 major protease (M).

Revisiting MMPBSA by Adoption of MC-Based Surface Area/Volume, ANI-ML Potentials, and Two-Valued Interior Dielectric Constant.

Here, we report the accuracy improvements of molecular mechanics Poisson-Boltzmann surface area (MMPBSA) calculations by adoption of ANI-ML potentials in replacement of MM terms, the use of solvent-accessible surface area (SASA) and volume (SAV) values from the Monte Carlo sampling of the probe, and introducing two different interior dielectric constants for electrostatic interactions of protein-ligand (P-L) and polar solvation term in the MMPBSA calculations. Our results show that the Pearson correlation coefficients of MMPBSA-calculated values with respect to experimental binding free energies can be drastically improved from 0.48 to 0.

The performance of ANI-ML potentials for ligand-n(H O) interaction energies and estimation of hydration free energies from end-point MD simulations.

Here, we investigate the performance of "Accurate NeurAl networK engINe for Molecular Energies" (ANI), trained on small organic compounds, on bulk systems including non-covalent interactions and applicability to estimate solvation (hydration) free energies using the interaction between the ligand and explicit solvent (water) from single-step MD simulations. The method is adopted from ANI using the Atomic Simulation Environment (ASE) and predicts the non-covalent interaction energies at the accuracy of wb97x/6-31G(d) level by a simple linear scaling for the conformations sampled by molecular dynamics (MD) simulations of ligand-n(H O) systems. For the first time, we test ANI potentials' abilities to reproduce solvation free energies using linear interaction energy (LIE) formulism by modifying the original LIE equation.

Accurate Binding Free Energy Method from End-State MD Simulations.

Herein, we introduce a new strategy to estimate binding free energies using end-state molecular dynamics simulation trajectories. The method is adopted from linear interaction energy (LIE) and ANI-2x neural network potentials (machine learning) for the atomic simulation environment (ASE). It predicts the single-point interaction energies between ligand-protein and ligand-solvent pairs at the accuracy of the wb97x/6-31G* level for the conformational space that is sampled by molecular dynamics (MD) simulations.

A neural network potential for the IRMOF series and its application for thermal and mechanical behaviors.

Metal-organic frameworks (MOFs) with their exceptional porous and organized structures have been the subject of numerous applications. Predicting the bulk properties from atomistic simulations requires the most accurate force fields, which is still a major problem due to MOFs' hybrid structures governed by covalent, ionic and dispersion forces. Application of molecular dynamics to such large periodic systems is thus beyond the current computational power.

Molecular dynamics simulations reveal the plausible agonism/antagonism mechanism by steroids on androgen receptor mutations.

Androgen receptors (AR) are the primary drug target in prostate cancer (PCa). There are several drugs developed against its activity for prostate cancer treatment, but cancer cells revive AR signaling against those drugs by using alternative steroids such as glucocorticoids. In addition, antagonists become agonists due to emergence of mutations in AR gene.

Experimental and theoretical investigation of water-soluble silicon(IV) phthalocyanine and its interaction with bovine serum albumin.

Photodynamic therapy (PDT) has drawn a great scientific attention to cancer treatment over the last decades. However, the bottleneck for the PDT is to find good photosensitizers (PSs) with greater water solubility, no aggregation, and fast discharge from the body. Therefore, there are still a big scientific desire for the synthesizing new rational PSs for treatment of cancer by PDT technique.

Rotational Thromboelastometry Profile in Children With Chronic Spontaneous Urticaria.

The pathogenesis of chronic spontaneous urticaria (CSU) is incompletely understood. There is a growing interest in the role of the coagulation cascade in chronic urticaria. Rotational thromboelastometry (ROTEM) assay enables the global assessment of coagulation status.

In Silico Investigation into H Uptake in MOFs: Combined Text/Data Mining and Structural Calculations.

Metal-organic frameworks (MOFs) with high surface areas and adjustable lattice structures are attractive for gas storage and thus have been a great interest in research. Although tremendous amount of data on MOFs have been available in the literature, there are very few studies considering methodological approach for H uptake properties of MOFs. In this study, we systematically investigated the H uptake capabilities of MOFs by means of text and data mining (TDM) through retrieving data of the surface areas (SA) and pore volumes (PV) from published manuscripts.

HBGA binding modes and selectivity in noroviruses upon mutation: a docking and molecular dynamics study.

Norovirus, also called winter vomiting bug, is the most common cause for gastroenteritis and severe childhood diarrhea disease. High mutation rates cause drug resistance and thus complicate the development of an effective therapeutics against virus infection. The virus protein enters the host cell via the interaction with histo-blood group antigens (HBGAs), formed by oligosaccharides.

Presence of a single nucleotide polymorphism (RS3758581) in a boy with DRESS syndrome.

Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a rare, potentially life-threatening, drug-induced hypersensitivity reaction that includes rash, hematologic abnormalities, lymphadenopathy, and internal organ involvement. The pathogenesis of DRESS syndrome is partially understood. Various medications have been described as the cause of DRESS syndrome.

Docking, molecular dynamics and free energy studies on aspartoacylase mutations involved in Canavan disease.

The disruption of aspartoacylase enzyme's catalytic activity causes fatal neurodegenerative Canavan disease. By molecular dynamics and docking methods, here we studied two deleterious mutations that have been identified in the Canavan patients' genotype E285A, F295S, and revealed the possible cause for the enzyme inhibition due to the drastic changes in active site dynamics, loss of interactions among Arg 71, Arg 168 and the substrate and pKa value of critical Glu178 residue. In addition to changes in the enzyme dynamics, free energy calculations show that the binding energy of substrate decreases dramatically up on mutations.

Thromboelastogram as a Tool to Predict Hypercoagulability in Children With Cystic Fibrosis.

Increased thrombophilic tendency in patients with cystic fibrosis (CF) has recently been reported. The determinants of thrombosis in children with CF remain largely unknown. Our aim in this study was to evaluate the thromboelastography (TEG) profile of children with CF through ROTEM (whole blood rotation thromboelastometry).

Computational insights into the protonation states of catalytic dyad in BACE1-acyl guanidine based inhibitor complex.

Developing small compound based drugs targeting the β-secretase (BACE) enzyme is one of the most promising strategies in treatment of the Alzheimer's disease. As the enzyme shows the activity based on the acid-base reaction at a very narrow pH range, the protonation state of aspartic acids with the residue number 32 and 228 (Asp32 and Asp228), which forms the active site dyad, along with the protonation state of the ligand (substrate or inhibitor) play very critical role in interactions between the ligand and enzyme. Thus, understanding the nature of the protonation state of both enzyme's active site dyad and ligand is crucial for drug design in Alzheimer's disease field.

Health-care conditions in elementary schools and teachers' knowledge of childhood asthma.

Background: For the adequate control of asthma in school-age children, it is recommended that teachers, school health personnel and administrators should have sufficient knowledge of how to manage asthma during school hours.

Aim: To investigate asthma health care in elementary schools, and teachers' knowledge of childhood asthma and its management.

Methods: The extent of knowledge of childhood asthma in 2779 teachers in 141 elementary schools (children aged 6-14, grades 1-8) in Bursa, the fourth largest city in Turkey, was evaluated.

Vibrational Spectroscopy Reveals Varying Structural Motifs in Cu(+)(CH4)(n) and Ag(+)(CH4)(n) (n = 1-6).

Vibrational spectra are measured for Cu(+)(CH4)(Ar)2, Cu(+)(CH4)2(Ar), Cu(+)(CH4)n (n = 3-6), and Ag(+)(CH4)n (n = 1-6) in the C-H stretching region (2500-3100 cm(-1)) using photofragment spectroscopy. Spectra are obtained by monitoring loss of Ar or CH4. Interaction with the metal ion produces substantial red shifts in the C-H stretches of proximate hydrogens.

Vibrational spectroscopy and theory of Fe2(+)(CH4)(n) (n = 1-3).

Vibrational spectra are measured for Fe2(+)(CH4)n (n = 1-3) in the C-H stretching region (2650-3100 cm(-1)) using photofragment spectroscopy, by monitoring the loss of CH4. All of the spectra exhibit an intense peak corresponding to the symmetric C-H stretch around 2800 cm(-1). The presence of a single peak suggests a nearly equivalent interaction between the iron dimer and the methane ligands.

Nasal and bronchial response to exercise in children with seasonal allergic rhinitis out of the pollen season.

Background: Allergic rhinitis is a type I allergic disease of the nasal mucosa, and is characterized by paroxysmal sneezing, watery rhinorrhea, and nasal blockage. In seasonal allergic rhinitis subjects, even subthreshold allergen doses have been found to cause inflammatory cell infiltration in the nasal mucosa. This study aimed to investigate the presence of nasal obstructions and symptoms in seasonal allergic rhinitis subjects by assessing an exercise challenge test (ECT) outside of the pollen season.

Near ultraviolet photodissociation spectroscopy of Mn(+)(H2O) and Mn(+)(D2O).

The electronic spectra of Mn(+)(H2O) and Mn(+)(D2O) have been measured from 30,000 to 35,000 cm(-1) using photodissociation spectroscopy. Transitions are observed from the (7)A1 ground state in which the Mn(+) is in a 3d(5)4s(1) electronic configuration, to the (7)B2 (3d(5)4py) and (7)B1 (3d(5)4px) excited states with T0 = 30,210 and 32,274 cm(-1), respectively. Each electronic transition has partially resolved rotational and extensive vibrational structure with an extended progression in the metal-ligand stretch at a frequency of ∼450 cm(-1).

Familial eosinophilic granulomatosis with polyangiitis in a mother and daughter.

A 17-year-old girl was admitted to our unit with weight loss, dyspnoea, arthralgia and sinusitis. Her medical history was noteworthy for bronchial asthma and she required systemic steroid therapy. Her mother had a history of eosinophilic granulomatosis with polyangiitis (EGPA).

Vibrational spectroscopy of Co⁺(CH₄)n and Ni⁺(CH₄)n (n = 1-4).

Vibrational spectra of M(+)(CH4)m(Ar)(3-m) and M(+)(CH4)n (M = Co, Ni; m = 1, 2; n = 3, 4) in the C-H stretching region (2500-3100 cm(-1)) are measured using photofragment spectroscopy, monitoring the loss of argon or methane. Interaction with the metal leads to large red shifts in the C-H stretches for proximate hydrogens. The extent of this shift is sensitive to the coordination (η(2) vs η(3)) and to the metal-methane distance.