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Accurate prediction of ligand-receptor binding affinity is crucial in structure-based drug design, significantly impacting the development of effective drugs. Recent advances in machine learning (ML)–based scoring functions have improved these predictions, yet challenges remain in modeling complex molecular interactions. This study introduces the AGL-EAT-Score, a scoring function that integrates extended atom-type multiscale weighted colored subgraphs with algebraic graph theory. This approach leverages the eigenvalues and eigenvectors of graph Laplacian and adjacency matrices to capture high-level details of specific atom pairwise interactions. Evaluated against benchmark datasets such as CASF-2016, CASF-2013, and the Cathepsin S dataset, the AGL-EAT-Score demonstrates notable accuracy, outperforming existing traditional and ML-based methods. The model's strength lies in its comprehensive similarity analysis, examining protein sequence, ligand structure, and binding site similarities, thus ensuring minimal bias and over-representation in the training sets. The use of extended atom types in graph coloring enhances the model's capability to capture the intricacies of protein-ligand interactions. The AGL-EAT-Score marks a significant advancement in drug design, offering a tool that could potentially refine and accelerate the drug discovery process. Scientific Contribution The AGL-EAT-Score presents an algebraic graph-based framework that predicts ligand-receptor binding affinity by constructing multiscale weighted colored subgraphs from the 3D structure of protein-ligand complexes. It improves prediction accuracy by modeling interactions between extended atom types, addressing challenges like dataset bias and over-representation. Benchmark evaluations demonstrate that AGL-EAT-Score outperforms existing methods, offering a robust and systematic tool for structure-based drug design. [ABSTRACT FROM AUTHOR]

Tropomyosin kinase receptor B (TrkB) has been explored as a therapeutic target for neurological and psychiatric disorders. However, the development of TrkB agonists was hindered by our poor understanding of the TrkB agonist binding location and affinity (both affect the regulation of disorder types). This motivated us to develop a combined computational and experimental approach to study TrkB binders. First, we developed a docking method to simulate the binding affinity of TrkB and binders identified by our magnetic drug screening platform from Gotu kola extracts. The Fred Docking scores from the docking computation showed strong agreement with the experimental results. Subsequently, using this screening platform, we identified a list of compounds from the NIH clinical collection library and applied the same docking studies. From the Fred Docking scores, we selected two compounds for TrkB activation tests. Interestingly, the ability of the compounds to increase dendritic arborization in hippocampal neurons matched well with the computational results. Finally, we performed a detailed binding analysis of the top candidates and compared them with the best-characterized TrkB agonist, 7,8-dyhydroxyflavon. The screening platform directly identifies TrkB binders, and the computational approach allows for the quick selection of top candidates with potential biological activities based on the docking scores. [ABSTRACT FROM AUTHOR]

Processing is one of the important and crucial parts that has been applied in traditional oriental medicine for a long time. The traditional ingredients were processed on the basis of the Yin Yang theory, Five Elements theory, and folk experiences. Among many processing techniques, honey-frying is a process enhancing the effects of traditional herbs on the Spleen and Stomach organs. This report provides an overview of the differences between chemical constituents and pharmacological activities of some traditional ingredients before and after roasting with honey. [ABSTRACT FROM AUTHOR]

Based on the first-order shear deformation theory taking into account geometrical nonlinearity, initial geometrical imperfection, vibration and nonlinear dynamic analysis of the sandwich laminated composite panel characterized by a continuous thickness variation in thermal environment and resting on an elastic foundation are considered in this paper. Variable thickness could affect the design of composite panel since it allows to tailor the stiffness features in the most stressed areas within the domain, keeping the weight constant. As a consequence, an improved dynamic behavior of the structure may be exhibited. The motion equations of dynamic analysis are determined due to Galerkin method and the obtained equation is numerically solved by using Runge–Kutta method. In numerical results, the effects of initial geometrical imperfections and geometrical parameters, material properties, coefficients of foundation, mechanical loads, temperature and the variable thickness on the nonlinear dynamic response and vibration of the laminated composite panel are investigated. [ABSTRACT FROM AUTHOR]

Poisson-Boltzmann (PB) model is one of the most popular implicit solvent models in biophysical modeling and computation. The ability of providing accurate and reliable PB estimation of electrostatic solvation free energy [ABSTRACT FROM AUTHOR]

This article explores the impact of surface area, volume, curvature, and Lennard-Jones (LJ) potential on solvation free energy predictions. Rigidity surfaces are utilized to generate robust analytical expressions for maximum, minimum, mean, and Gaussian curvatures of solvent-solute interfaces, and define a generalized Poisson-Boltzmann (GPB) equation with a smooth dielectric profile. Extensive correlation analysis is performed to examine the linear dependence of surface area, surface enclosed volume, maximum curvature, minimum curvature, mean curvature, and Gaussian curvature for solvation modeling. It is found that surface area and surfaces enclosed volumes are highly correlated to each other's, and poorly correlated to various curvatures for six test sets of molecules. Different curvatures are weakly correlated to each other for six test sets of molecules, but are strongly correlated to each other within each test set of molecules. Based on correlation analysis, we construct twenty six nontrivial nonpolar solvation models. Our numerical results reveal that the LJ potential plays a vital role in nonpolar solvation modeling, especially for molecules involving strong van der Waals interactions. It is found that curvatures are at least as important as surface area or surface enclosed volume in nonpolar solvation modeling. In conjugation with the GPB model, various curvature-based nonpolar solvation models are shown to offer some of the best solvation free energy predictions for a wide range of test sets. For example, root mean square errors from a model constituting surface area, volume, mean curvature, and LJ potential are less than 0.42 kcal/mol for all test sets. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The need for more reliable and radiation hard complementary metal-oxide-semiconductor compatible devices coupled with an ever increasing shrinkage of device dimensions has led naturally to interest in metal-oxide semiconductor field-effect transistors having nontraditional geometries. One such geometry is the gate-all-around transistor, which has been suggested to be less sensitive than its planar counterpart to the effect of charge build-up at the semiconductor-insulator interface such as that induced by irradiation. In order to explore the radiation hardness of such a structure, the effect of radiation on gate-all-around n-type metal-oxide-semiconductor devices was investigated by computing the effect of charging on the threshold voltage of the device. The radiation sensitivity in ideal structures is explored, and the greater radiation sensitivity found experimentally in some devices is explained. [ABSTRACT FROM AUTHOR]

The authors have used transient photovoltage measurements to evaluate carrier relaxation times (τ) in P3HT:PCBM based photocells over a wide range of open circuit voltages. Satisfactory agreement is found with data obtained by low frequency impedance measurements. The authors find the differential capacitance measurements yield data consistent with the theoretical value expected based on Langevin recombination. The Langevin coefficient is three orders of magnitude smaller than the theoretical one. For the low light levels, the relaxation time variation is determined by the RC time constant behavior of the photodiode. [ABSTRACT FROM AUTHOR]

The authors have examined ionizing radiation effects in the organic photovoltaic material poly(3-hexylthiophene):([6, 6]-phenyl C61 butyric acid methyl ester) for total accumulated doses up to 300 krad(SiO2). The authors find that the open circuit voltage varies with the accumulation of irradiation; however, the other parameters such as relaxation time, short circuit current, and charge carrier density remain to first order constant. This behavior is inconsistent with observations on preirradiation devices in which all depend directly on the open circuit voltage. [ABSTRACT FROM AUTHOR]

The removal rates of organics and nutrients in municipal wastewater were examined using a laboratory-scale Anaerobic/Anoxic/Oxic (A2O) process modified with fiber polypropylene media at different operational conditions. The system demonstrated excellent performance with the removal rates of chemical oxygen demand (COD), total nitrogen (TN) and total phosphorous (TP) ranging from 91% to 98%, from 48% to 63%, and from 56% to 71%, respectively. Our system was superior to those previously reported based on more complex biofilm reactors, particularly from an economic point of view. For our system, a considerable reduction of COD (55%-68%) occurred even in the anaerobic reactor. The removal rates of COD and nutrients exhibited a slight decreasing trend with a higher organic loading rate (OLR) (0.5 to 2.2 kg COD m-3day-1) or with a shorter hydraulic retention time (HRT). The results may be attributed to the competition between nitrifying and heterotrophic bacteria and/or the insufficient time for biological uptake. It is expected that applying fiber polypropylene media to a conventional A2O process may significantly enhance the treatment efficacy of organics and nutrients as a cost-effective strategy. [ABSTRACT FROM AUTHOR]

A novel measurement technique is used to extract two physically distinct 'permanent' (long lived on our experimental time scale, ≤12 000 s) and one recoverable charge components of the negative bias temperature instability in p-channel metal-oxide-semiconductor field effect transistors under inversion and n-channel devices under accumulation. The results suggest that the permanent components are present in both cases, while there is little, if any, recoverable charge present in the case of the n-channel device. A physical explanation is provided involving the band energy diagram to explain these observations. [ABSTRACT FROM AUTHOR]