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This paper presents a method of moments (MoM) formulation for large thin-wire structures. In our approach, a modified version of the well-known Rao–Wilton–Glisson (RWG) basis functions for wires including a linear phase term is considered. This additional term allows an efficient representation of the travelling-wave modes on each wire, while it preserves the main advantages of RWG bases for arbitrarily complex wire topologies. The paper contains a detailed description of the algorithm used for the computation of the impedance matrix integrals. Finally, some results for scattering problems are presented to show the agreement with the conventional RWG-MoM solution. © 2006 Wiley Periodicals, Inc. Microwave Opt Technol Lett 48: 960–966, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.21533 [ABSTRACT FROM AUTHOR]

A comparative study of the products of the cell cycle control genes p53 (mutated form), p21 , Rb (nonphosphorylated and phosphorylated form) and TGFß was performed by immunohistochemistry and Western blot, in benign breast disorders and breast cancer (in situ and infiltrating tumors). For the five proteins studied, the relative numbers of positively stained cells were higher in in situ carcinoma than in benign breast diseases. In infiltrating breast tumors, the relative numbers of positively stained cells were even higher than in in situ tumors except for the percentage of pRb immunostained cells, which decreased slightly in infiltrative tumors. For the other four proteins, the percentages of positively stained cases were similar to those found in in situ tumors. In the three groups of patients, TGFß immunoreaction appeared in the cytoplasm while immunoreactions to p53 , p21 , Rb, and pRb were found always in the nucleus except for p21 in in situ tumors, which showed cytoplasmic immunoreaction. Present results suggest that accumulation of mutated p53 , cytoplasmic p21 , and pRb in breast gland epithelium might be a crucial point in the development of in situ adenocarcinoma. In the infiltrating tumors, the expression of p21 in the nuclei and the decrease in pRb expression suggest an insufficient attempt to hinder cell proliferation. [ABSTRACT FROM AUTHOR]

A linear-phase term is incorporated into the triangular-type Rao–Wilton–Glisson (RWG) vector basis functions in the method of moments (MoM) formulation. The objective consists of including the dominant phase variation of the current density within the basis-functions formulation, thus allowing an efficient representation of the induced current on large bodies using fewer unknowns. Assuming a good estimation of the phase variation, the new MoM formulation with linearly-phased RWG basis functions is shown to greatly relieve the storage and solution time of the conventional MoM with RWG basis functions, while accurately reproducing the scattered fields of some chosen problems. © 2004 Wiley Periodicals, Inc. Microwave Opt Technol Lett 44: 106–112, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.20560 [ABSTRACT FROM AUTHOR]

A structural and vibrational study of amino acid serine in aqueous solution has been carried out using Fourier transform spectroscopies and quantum mechanical calculations. FT-IR and FT-Raman spectra of serine in H2O and D2O solutions were recorded and a general assignment of the observed bands was proposed on the basis of a zwitterionic structure for serine. Main criteria were the observed wavenumber shifts upon deuteration and previous assignments for other amino acids. A quadratic force field was computed using ab initio methodology at the 6-31+G** level and the hybrid functional B3LYP. The solvent effect was simulated by placing the serine molecule into an ellipsoidal cavity surrounded by a continuum solvent characterized by its dielectric constant. The solute–solvent electrostatic interaction was evaluated by means a multipolar moment expansion introduced in the Hamiltonian. The ab initio force field was obtained from the analytical second derivatives of the molecular geometry evaluated in a point of minimal energy, which was reached under the same calculation methodology. The optimized structural parameters were compared to those reported for l-serine crystal, which confirmed the zwitterionic structure for this molecule in aqueous solution. Ab initio force constants in cartesian coordinates were transformed into a set of locally symmetrized internal coordinates, thus allowing for a scaling procedure using two generic factors. Normal mode description was obtained as the potential energy distribution. The scaled wavenumbers were compared with those experimental in order to check the previous assignments. It also allowed us to add new data to the sets of experimental wavenumbers. Infrared intensities were calculated for both, H2O and D2O solutions, and compared to the experimental intensities. [Copyright &y& Elsevier]

We investigate the inhibition mechanism between pomotrelvir and the SARS-CoV-2 main protease using molecular mechanics and quantum mechanics/molecular mechanics simulations. Alchemical transformations where each Pi group of pomotrelvir was transformed into its counterpart in nirmatrelvir were performed to unravel the individual contribution of each group to the binding and reaction processes. We have shown that while a γ-lactam ring is preferred at position P1, a δ-lactam ring is a good alternative for the design of inhibitors for variants presenting mutations at position 166. For the P2 position, tertiary amines are preferred with respect to secondary amines. Flexible side chains at the P2 position can disrupt the preorganization of the active site, favouring the exploration of non-reactive conformations. The substitution of the P2 group of pomotrelvir by that of nirmatrelvir resulted in a compound, named as C2, that presents a better binding free energy and a higher population of reactive conformations in the Michaelis complex. Analysis of the chemical reaction to form the covalent complex has shown a similar reaction mechanism and activation free energies for pomotrelvir, nirmatrelvir and C2. We hope that these findings could be useful to design better inhibitors to fight present and future variants of the SARS-CoV-2 virus., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

We present in this work the emle-engine package (https://github.com/chemle/emle-engine)─the implementation of a new machine learning embedding scheme for hybrid machine learning potential/molecular-mechanics (ML/MM) dynamics simulations. The package is based on an embedding scheme that uses a physics-based model of the electronic density and induction with a handful of tunable parameters derived from in vacuo properties of the subsystem to be embedded. This scheme is completely independent of the in vacuo potential and requires only the positions of the atoms of the machine learning subsystem and the positions and partial charges of the molecular mechanics environment. These characteristics allow emle-engine to be employed in existing QM/MM software. We demonstrate that the implemented electrostatic machine learning embedding scheme (named EMLE) is stable in enhanced sampling molecular dynamics simulations. Through the calculation of free energy surfaces of alanine dipeptide in water with two different ML options for the in vacuo potential and three embedding models, we test the performance of EMLE. When compared to the reference DFT/MM surface, the EMLE embedding is clearly superior to the MM one based on fixed partial charges. The configurational dependence of the electronic density and the inclusion of the induction energy introduced by the EMLE model leads to a systematic reduction in the average error of the free energy surface when compared to MM embedding. By enabling the usage of EMLE embedding in practical ML/MM simulations, emle-engine will make it possible to accurately model systems and processes that feature significant variations in the charge distribution of the ML subsystem and/or the interacting environment.

Ubiquitin-specific protease 7 (USP7) is a deubiquitinase enzyme that plays a critical role in regulating various cellular processes by cleaving ubiquitin molecules from target proteins. The C-terminal loop (CTL) motif is a specific region at the C-terminal end of the USP7 enzyme. Recent experiments suggest that the CTL motif plays a role in USP7's catalytic activity by contributing to the enzyme's structural stability, substrate recognition, and catalytic efficiency. The objective of this work is to elucidate these roles through the utilization of computational methods for molecular simulations. For this, we conducted extensive molecular dynamics (MD) simulations to investigate the conformational dynamics and protein-protein interactions within the USP7 enzyme-substrate complex with the substrate consisting of the ubiquitin tagged with the fluorescent label rhodamine 110-gly (Ub-Rho). Our results demonstrate that the CTL motif plays a crucial role in stabilizing the Ubl domains' conformation and augmenting the stability of active conformations within the enzyme-substrate complex. Conversely, the absence of the CTL motif results in increased flexibility and variability in Ubl domains' motion, leading to a reduced percentage of active conformations. Furthermore, our analysis of protein-protein interactions highlights the significance of the CTL motif in anchoring the Ubl45 domains to the catalytic domain (CD), thereby facilitating stable interactions with the substrate. Overall, our findings provide valuable insights into the conformational dynamics and protein-protein interactions inherent in the USP7 enzyme-substrate complex. These insights shed light on some mechanistic details of USP7 concerning the substrate's recognition before its catalytic action.