SARS-CoV-2 Spike Protein Interaction Space.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a +sense single-strand RNA virus. The virus has four major surface proteins: spike (S), envelope (E), membrane (M), and nucleocapsid (N), respectively. The constitutive proteins present a high grade of symmetry.

Atoms-In-Molecules' Faces of Chemical Hardness by Conceptual Density Functional Theory.

The chemical hardness concept and its realization within the conceptual density functional theory is approached with innovative perspectives, such as the electronegativity and hardness equalization of atoms in molecules connected with the softness kernel, in order to examine the structure-reactivity equalization ansatz between the electronic sharing index and the charge transfer either in the additive or geometrical mean picture of bonding. On the other hand, the maximum hardness principle presents a relation with the chemical stability of the hardness concept. In light of the inverse relation between hardness and polarizability, the minimum polarizability principle has been proposed.

The Density Functional Theory Account of Interplaying Long-Range Exchange and Dispersion Effects in Supramolecular Assemblies of Aromatic Hydrocarbons with Spin.

Aromatic hydrocarbons with fused benzene rings and regular triangular shapes, called -triangulenes according to the number of rings on one edge, form groundstates with -1 unpaired spins because of topological reasons. Here, we focus on methodological aspects emerging from the density functional theory (DFT) treatments of dimer models of the = 2 triangulene (called also phenalenyl), observing that it poses interesting new problems to the issue of long-range corrections. Namely, the interaction comprises simultaneous spincoupling and van der Waals effects, i.

Three-Body Excitations in Fock-Space Coupled-Cluster: Fourth Order Perturbation Correction to Electron Affinity and Its Relation to Bondonic Formalism.

In this paper, we present a formulation of highly correlated Fock-space multi-reference coupled-cluster (FSMRCC) methods, including approximate triples on top of the FSMRCC with singles and doubles, which correct the electron affinities by at least at third and up to the fourth order in perturbation. We discuss various partial fourth-order schemes, which are reliable and yet computationally more efficient than the full fourth-order triples scheme. The third-order scheme is called MRCCSD+T(3).

Chemical Bonding by the Chemical Orthogonal Space of Reactivity.

The fashionable Parr-Pearson (PP) atoms-in-molecule/bonding (AIM/AIB) approach for determining the exchanged charge necessary for acquiring an equalized electronegativity within a chemical bond is refined and generalized here by introducing the concepts of chemical power within the chemical orthogonal space (COS) in terms of electronegativity and chemical hardness. Electronegativity and chemical hardness are conceptually orthogonal, since there are opposite tendencies in bonding, i.e.

Fock-Space Coupled Cluster Theory: Systematic Study of Partial Fourth Order Triples Schemes for Ionization Potential and Comparison with Bondonic Formalism.

In this paper, we have made a systematic study of partial fourth order perturbative schemes due to triples to compute the ionization potential within Fock-space multi-reference coupled-cluster theory. In particular, we have obtained computationally less expensive correlation schemes due to fourth order triples. Prototype examples have been considered to explore the efficacy of the approximate methods mentioned, while the bondonic formalism supporting the bonding phenomenology is also respectively for the first time here advanced.

Ld/Mm+ Simulation of Some Aristolochic and Humic Acids Species Coupled in Periodic Box with Water.

Background: This study is one of the dynamics molecular docking that presents the interactions between a molecular model of the mixture of humic acid structure and 18 aristolochic acid structures, from the PubChem database in a water box that simulates the environment reactions.

Objective: The major objective was to identify what happens in this procedure (LD/MM+) with the coupled species.

Methods: LD/MM+ SIMULATION (Langevin dynamics simulation).

Atoms in Generalized Orbital Configurations: Towards Atom-Dedicated Density Functionals.

Deriving a practical formula for the atomic body with generalized shell occupations, we perform a detective analysis of the radial distribution in the exchange energy, hinting at ideas about new types of density functionals, dedicated to the specifics of the electronic structure of atoms, exploiting the intrinsic spherical symmetry.

Neurotoxicity of Pesticides: The Roadmap for the Cubic Mode of Action.

Pesticides are used today on a planetary-wide scale. The rising need for substances with this biological activity due to an increasing consumption of agricultural and animal products and to the development of urban areas makes the chemical industry to constantly investigate new molecules or to improve the physicochemical characteristics, increase the biological activities and improve the toxicity profiles of the already known ones. Molecular databases are increasingly accessible for in vitro and in vivo bioavailability studies.

QSAR by Minimal Topological Difference[s]: Post-Modern Perspectives.

In the context of reconsidering the Quantitative Structure-Activity Relationship (QSAR) methods at the economical level, namely the optimization rules of OECD, the present review unfolds the key features of Minimal Sterical, Monte-Carlo and Minimal Topological Difference (MTD) methods, developed for quantitative treatment of the relations between biological activity of organic chemical compounds (drugs, pesticides, and so on) and their structures. The initial Minimal Steric Difference (MSD) is completed by the three-dimensional variant of the MTD method, being the last one referred to here, while the main principles of validating and guiding a viable QSAR method verified by the analytical-automated MTD, thus enlarging the perspectives of understanding the chemical-biological interaction at the level of ligand-receptor sites, cavity, and walls, with a true service to the future adaptive molecular design.

Ligand Shaping in Induced Fit Docking of MraY Inhibitors. Polynomial Discriminant and Laplacian Operator as Biological Activity Descriptors.

Docking-i.e., interaction of a small molecule (ligand) with a proteic structure (receptor)-represents the ground of drug action mechanism of the vast majority of bioactive chemicals.

Molecular Dynamic Studies of the Complex Polyethylenimine and Glucose Oxidase.

Glucose oxidase (GOx) is an enzyme produced by Aspergillus, Penicillium and other fungi species. It catalyzes the oxidation of β-d-glucose (by the molecular oxygen or other molecules, like quinones, in a higher oxidation state) to form d-glucono-1,5-lactone, which hydrolyses spontaneously to produce gluconic acid. A coproduct of this enzymatic reaction is hydrogen peroxide (H₂O₂).

Learning the Relationship between the Primary Structure of HIV Envelope Glycoproteins and Neutralization Activity of Particular Antibodies by Using Artificial Neural Networks.

The dependency between the primary structure of HIV envelope glycoproteins (ENV) and the neutralization data for given antibodies is very complicated and depends on a large number of factors, such as the binding affinity of a given antibody for a given ENV protein, and the intrinsic infection kinetics of the viral strain. This paper presents a first approach to learning these dependencies using an artificial feedforward neural network which is trained to learn from experimental data. The results presented here demonstrate that the trained neural network is able to generalize on new viral strains and to predict reliable values of neutralizing activities of given antibodies against HIV-1.

Hydractinia echinata test-system. IV. Toxic synergism of human pharmaceuticals in mixtures with iodoform.

The structure-toxicity relationships for a series of singular human stomatological pharmaceuticals preparations and in mixture with Iodoform on Hydractinia echinata were obtained and their synergism was analyzed through the Metamorphosis Reduction Concentration (MRC50) within the "Köln model". The differences manifested between the total and individual components of the samples and mixtures, associated with toxic versus non-toxic synergism, are dependent on three essential factors of synthesis (the nature, the concentration and the number) besides manifested isotoxicity of the given components. The method represents a practical alternative useful for the reduction of experimental tests on animal to the lowest possible level, in accordance to the '3Rs' (reduce, reuse and recycle) integrative concept.

Chemical Structure-Biological Activity Models for Pharmacophores' 3D-Interactions.

Within medicinal chemistry nowadays, the so-called pharmaco-dynamics seeks for qualitative (for understanding) and quantitative (for predicting) mechanisms/models by which given chemical structure or series of congeners actively act on biological sites either by focused interaction/therapy or by diffuse/hazardous influence. To this aim, the present review exposes three of the fertile directions in approaching the biological activity by chemical structural causes: the special computing trace of the algebraic structure-activity relationship (SPECTRAL-SAR) offering the full analytical counterpart for multi-variate computational regression, the minimal topological difference (MTD) as the revived precursor for comparative molecular field analyses (CoMFA) and comparative molecular similarity indices analysis (CoMSIA); all of these methods and algorithms were presented, discussed and exemplified on relevant chemical medicinal systems as proton pump inhibitors belonging to the 4-indolyl,2-guanidinothiazole class of derivatives blocking the acid secretion from parietal cells in the stomach, the 1-[(2-hydroxyethoxy)-methyl]-6-(phenylthio)thymine congeners' (HEPT ligands) antiviral activity against Human Immunodeficiency Virus of first type (HIV-1) and new pharmacophores in treating severe genetic disorders (like depression and psychosis), respectively, all involving 3D pharmacophore interactions.

Linear and Branched PEIs (Polyethylenimines) and Their Property Space.

A chemical property space defines the adaptability of a molecule to changing conditions and its interaction with other molecular systems determining a pharmacological response. Within a congeneric molecular series (compounds with the same derivatization algorithm and thus the same brute formula) the chemical properties vary in a monotonic manner, i.e.

Quantitative structure-activity/ecotoxicity relationships (QSAR/QEcoSAR) of a series of phosphonates.

In this paper the structure-toxicity relationship studies were performed for a series of 60 phosphonates. The toxicity of the compounds was determined by two ways: by quantifying the measured toxicity values, Mlog(1/MRIC50) collected by literature, for rodents species; second by using EcoSAR software version 1.11, for calculating the toxicity for fish species, considered as dependent variables and they were related to structural features obtained by molecular and quantum mechanics calculations.

Double Variational Binding--(SMILES) Conformational Analysis by Docking Mechanisms for Anti-HIV Pyrimidine Ligands.

Variational quantitative binding-conformational analysis for a series of anti-HIV pyrimidine-based ligands is advanced at the individual molecular level. This was achieved by employing ligand-receptor docking algorithms for each molecule in the 1,3-disubstituted uracil derivative series that was studied. Such computational algorithms were employed for analyzing both genuine molecular cases and their simplified molecular input line entry system (SMILES) transformations, which were created via the controlled breaking of chemical bonds, so as to generate the longest SMILES molecular chain (LoSMoC) and Branching SMILES (BraS) conformations.

Structure-biological function relationship extended to mitotic arrest-deficient 2-like protein Mad2 native and mutants-new opportunity for genetic disorder control.

Overexpression of mitotic arrest-deficient proteins Mad1 and Mad2, two components of spindle assembly checkpoint, is a risk factor for chromosomal instability (CIN) and a trigger of many genetic disorders. Mad2 transition from inactive open (O-Mad2) to active closed (C-Mad2) conformations or Mad2 binding to specific partners (cell-division cycle protein 20 (Cdc20) or Mad1) were targets of previous pharmacogenomics studies. Here, Mad2 binding to Cdc20 and the interconversion rate from open to closed Mad2 were predicted and the molecular features with a critical contribution to these processes were determined by extending the quantitative structure-activity relationship (QSAR) method to large-size proteins such as Mad2.

QSTR studies regarding the ECOSAR toxicity of benzene-carboxylic acid' esters to fathead minnow fish (Pimephales promelas).

The present work employs 152 benzene-carboxylic acid' esters having computed the toxicity within the range [2.251, 10.222] for fathead minnow fish (Pimephales promelas).

Mitotic checkpoint proteins Mad1 and Mad2 - structural and functional relationship with implication in genetic diseases.

In normal cells, the accuracy of chromosome segregation which assures cells euploidy depends on mitosis mechanics and on proper functioning of a specific complex of proteins represented by the error-checking spindle assembly checkpoint (SAC). SAC proteins are deeply involved in correct cell divisions, but some of these, such as mitotic arrest-deficient proteins (Mad1 and Mad2), are critical. Mad1 and Mad2 are involved in preventing "wrong" cellular divisions which lead to cellular aneuploidy and are recognized as inductors of genetic disorders, as well as activators of oncoproteins.

Bondonic effects in group-IV honeycomb nanoribbons with Stone-Wales topological defects.

This work advances the modeling of bondonic effects on graphenic and honeycomb structures, with an original two-fold generalization: (i) by employing the fourth order path integral bondonic formalism in considering the high order derivatives of the Wiener topological potential of those 1D systems; and (ii) by modeling a class of honeycomb defective structures starting from graphene, the carbon-based reference case, and then generalizing the treatment to Si (silicene), Ge (germanene), Sn (stannene) by using the fermionic two-degenerate statistical states function in terms of electronegativity. The honeycomb nanostructures present η-sized Stone-Wales topological defects, the isomeric dislocation dipoles originally called by authors Stone-Wales wave or SWw. For these defective nanoribbons the bondonic formalism foresees a specific phase-transition whose critical behavior shows typical bondonic fast critical time and bonding energies.

Koopmans' analysis of chemical hardness with spectral-like resolution.

Three approximation levels of Koopmans' theorem are explored and applied: the first referring to the inner quantum behavior of the orbitalic energies that depart from the genuine ones in Fock space when the wave-functions' Hilbert-Banach basis set is specified to solve the many-electronic spectra of spin-orbitals' eigenstates; it is the most subtle issue regarding Koopmans' theorem as it brings many critics and refutation in the last decades, yet it is shown here as an irrefutable "observational" effect through computation, specific to any in silico spectra of an eigenproblem; the second level assumes the "frozen spin-orbitals" approximation during the extracting or adding of electrons to the frontier of the chemical system through the ionization and affinity processes, respectively; this approximation is nevertheless workable for great deal of chemical compounds, especially organic systems, and is justified for chemical reactivity and aromaticity hierarchies in an homologue series; the third and the most severe approximation regards the extension of the second one to superior orders of ionization and affinities, here studied at the level of chemical hardness compact-finite expressions up to spectral-like resolution for a paradigmatic set of aromatic carbohydrates.