Evaluation of DFT methods for predicting geometries and NMR spectra of Bi(III) dithiocarbamate complexes with antitumor properties.

Context: Bismuth complexes with dithiocarbamate ligands have attracted attention because of their biological applications, such as antimicrobial, antileishmanial, and anticancer properties. These complexes have high cytotoxic activity against cancer cells, being more active than the standard drugs cisplatin, doxorubicin, and tamoxifen. In the present study, we investigated the ability of some DFT methods to reproduce the geometries and NMR spectra of the Bi(III) dithiocarbamate complexes, selected based on their proven antitumor activity.

Antiviral Activity of Flavonoids from Geopropolis of the Brazilian Jandaira Bee against Zika and Dengue Viruses.

Arthropod-borne viruses within the family such as Zika (ZIKV) and dengue (DENV) are responsible for major outbreaks in tropical countries, and there are no specific treatments against them. Naringenin and 7--methyl naringenin are flavonoids that can be extracted from geopropolis, a natural material that the Brazilian Jandaira stingless bee (Melipona subnitida Ducke) produces to protect its nest. Here, these flavonoids were tested against ZIKV and DENV using Vero cells as a cellular model to perform a cytotoxicity assay and to define the effective concentrations of TCID as the readout method.

Quantum chemical descriptors based on semiempirical methods for large biomolecules.

In this Review, we reviewed the efforts to expand the applications of conceptual density functional theory reactivity descriptors and hard and soft acid and base principles for macromolecules and other strategies that focused on low-level quantum chemistry methods. Currently, recent applications are taking advantage of modifications of these descriptors using semiempirical electronic structures to explain enzymatic catalysis reactions, protein-binding processes, and structural analysis in proteins. We have explored these new solutions along with their implementations in the software PRIMoRDiA, discussing their impact on the field and its perspectives.

Investigation of the structural dynamics of a knotted protein and its unknotted analog using molecular dynamics.

The role of knots in proteins remains elusive. Some studies suggest an impact on stability; the difficulty in comparing systems to assess this effect, however, has been a significant challenge. In this study, we produced and analyzed molecular dynamic trajectories considering three different temperatures of two variants of ornithine transcarbamylase (OTC), only one of which has a 3 knot, in order to evaluate the relative stability of the two molecules.

A higher flexibility at the SARS-CoV-2 main protease active site compared to SARS-CoV and its potentialities for new inhibitor virtual screening targeting multi-conformers.

The main-protease (M) catalyzes a crucial step for the SARS-CoV-2 life cycle. The recent SARS-CoV-2 presents the main protease (M) with 12 mutations compared to SARS-CoV (M). Recent studies point out that these subtle differences lead to mobility variances at the active site loops with functional implications.

Thermochemical and Quantum Descriptor Calculations for Gaining Insight into Ricin Toxin A (RTA) Inhibitors.

In this work, we performed a study to assess the interactions between the ricin toxin A (RTA) subunit of ricin and some of its inhibitors using modern semiempirical quantum chemistry and ONIOM quantum mechanics/molecular mechanics (QM/MM) methods. Two approaches were followed (calculation of binding enthalpies, Δ , and reactivity quantum chemical descriptors) and compared with the respective half-maximal inhibitory concentration (IC) experimental data, to gain insight into RTA inhibitors and verify which quantum chemical method would better describe RTA-ligand interactions. The geometries for all RTA-ligand complexes were obtained after running classical molecular dynamics simulations in aqueous media.

Discovery of RTA ricin subunit inhibitors: a computational study using PM7 quantum chemical method and steered molecular dynamics.

Ricin is a potent toxin derived from the castor bean plant and comprises two subunits, RTA and RTB. Because of its cytotoxicity, ricin has alarmed world authorities for its potential use as a chemical weapon. Ricin also affects castor bean agribusiness, given the risk of animal and human poisoning.

PRIMoRDiA: A Software to Explore Reactivity and Electronic Structure in Large Biomolecules.

Plenty of enzymes with structural data do not have their mechanism of catalysis elucidated. Reactivity descriptors, theoretical quantities generated from resolved electronic structure, provide a way to predict and rationalize chemical processes of such systems. In this Application Note, we present PRIMoRDiA (MoRDiA acromolecular eactivity escriptors ccess), a software built to calculate the reactivity descriptors of large biosystems by employing an efficient and accurate treatment of the large output files produced by quantum chemistry packages.

GPU algorithms for density matrix methods on MOPAC: linear scaling electronic structure calculations for large molecular systems.

Purification of the density matrix methods should be employed when dealing with complex chemical systems containing many atoms. The running times for these methods scale linearly with the number of atoms if we consider the sparsity from the density matrix. Since the efficiency expected from those methods is closely tied to the underlying parallel implementations of the linear algebra operations (e.

Theoretical characterization of the shikimate 5-dehydrogenase reaction from Mycobacterium tuberculosis by hybrid QC/MM simulations and quantum chemical descriptors.

In this study, we have investigated the enzyme shikimate 5-dehydrogenase from the causative agent of tuberculosis, Mycobacterium tuberculosis. We have employed a mixture of computational techniques, including molecular dynamics, hybrid quantum chemical/molecular mechanical potentials, relaxed surface scans, quantum chemical descriptors and free-energy simulations, to elucidate the enzyme's reaction pathway. Overall, we find a two-step mechanism, with a single transition state, that proceeds by an energetically uphill hydride transfer, followed by an energetically downhill proton transfer.

Repurposing approved drugs as inhibitors of SARS-CoV-2 S-protein from molecular modeling and virtual screening.

Herein, molecular modeling techniques were used with the main goal to obtain candidates from a drug database as potential targets to be used against SARS-CoV-2. This novel coronavirus, responsible by the COVID-19 outbreak since the end of 2019, became a challenge since there is not vaccine for this disease. The first step in this investigation was to solvate the isolated S-protein in water for molecular dynamics (MD) simulation, being observed a transition from "up" to "down" conformation of receptor-binding domain (RBD) of the S-protein with angle of 54.

Semiempirical methods do Fukui functions: Unlocking a modeling framework for biosystems.

Obtaining reactivity information from the molecular electronic structure of a chemical system is a computationally intensive process. As a way of probing reactivity information around that, there exist electron density response variables, such as the Fukui functions (FFs), which are well-established descriptors that summarize the local susceptibility to react. These properties only require few single-point quantum chemical calculations, but even then, the intrinsic high cost and unfavorable computational complexity with respect to the number of atoms in the system makes this approach available only to small fragments and systems.

Elucidating Enzymatic Catalysis Using Fast Quantum Chemical Descriptors.

In general, computational simulations of enzymatic catalysis processes are thermodynamic and structural surveys to complement experimental studies, requiring high level computational methods to match accurate energy values. In the present work, we propose the usage of reactivity descriptors, theoretical quantities calculated from the electronic structure, to characterize enzymatic catalysis outlining its reaction profile using low-level computational methods, such as semiempirical Hamiltonians. We simulate three enzymatic reactions paths, one containing two reaction coordinates and without prior computational study performed, and calculate the reactivity descriptors for all obtained structures.

Efficient algorithm for expanding theoretical electron densities in canterakis-zernike functions.

An algorithm for the efficient computation of Canterakis-Zernike moments of theoretically computed molecular electron densities and rotationally invariant Fingerprint indices derived from them is reported. The algorithm is suitable for any density expressed in terms of Gaussian- or Slater-type functions within the Linear Combination of Atomic Orbitals framework at any level of computation. Electron density is expressed as a one-center expansion of real regular spherical harmonics times radial factors by means of translation techniques, which facilitates the efficient computation of the moments in terms of a single one-dimension numerical integration.

Determining the Relative Binding Affinity of Ricin Toxin A Inhibitors by Using Molecular Docking and Nonequilibrium Work.

Ricin is a ribosome-inactivating protein (RIP type 2) consisting of two subunits, ricin toxin A (RTA) and ricin toxin B (RTB). Because of its cytotoxicity, ricin has worried world authorities for its potential use as a chemical weapon; therefore, its inhibition is of great biotechnological interest. RTA is the target for inhibitor synthesis, and pterin derivatives are promising candidates to inhibit it.

NAMD goes quantum: an integrative suite for hybrid simulations.

Hybrid methods that combine quantum mechanics (QM) and molecular mechanics (MM) can be applied to studies of reaction mechanisms in locations ranging from active sites of small enzymes to multiple sites in large bioenergetic complexes. By combining the widely used molecular dynamics and visualization programs NAMD and VMD with the quantum chemistry packages ORCA and MOPAC, we created an integrated, comprehensive, customizable, and easy-to-use suite (http://www.ks.

Assessment of semiempirical enthalpy of formation in solution as an effective energy function to discriminate native-like structures in protein decoy sets.

In this work, we tested the PM6, PM6-DH+, PM6-D3, and PM7 enthalpies of formation in aqueous solution as scoring functions across 33 decoy sets to discriminate native structures or good models in a decoy set. In each set these semiempirical quantum chemistry methods were compared according to enthalpic and geometric criteria. Enthalpically, we compared the methods according to how much lower was the enthalpy of each native, when compared with the mean enthalpy of its set.

Parameters for the RM1 Quantum Chemical Calculation of Complexes of the Trications of Thulium, Ytterbium and Lutetium.

The RM1 quantum chemical model for the calculation of complexes of Tm(III), Yb(III) and Lu(III) is advanced. Subsequently, we tested the models by fully optimizing the geometries of 126 complexes. We then compared the optimized structures with known crystallographic ones from the Cambridge Structural Database.

A topological assessment of the electronic structure of mesoionic compounds.

Mesoionic compounds belonging to the 1,3-oxazol-5-one, 1,3-diazole-4-thione and 1,3-thiazole-5-thione rings have been evaluated by a combination of Density Functional Theory, Quantum Theory of Atoms in Molecules, Electron Localization Function, Natural Bond Orbitals and Geodesic Electrostatic Potential Charge calculations. Atomic, bond, and ring properties have been considered to describe the electronic structure of mesoionic compounds. The results show that not only the ring type, but also the substituent groups have great influence on these properties.

RM1 Semiempirical Quantum Chemistry: Parameters for Trivalent Lanthanum, Cerium and Praseodymium.

The RM1 model for the lanthanides is parameterized for complexes of the trications of lanthanum, cerium, and praseodymium. The semiempirical quantum chemical model core stands for the [Xe]4fn electronic configuration, with n =0,1,2 for La(III), Ce(III), and Pr(III), respectively. In addition, the valence shell is described by three electrons in a set of 5d, 6s, and 6p orbitals.

RM1 Model for the Prediction of Geometries of Complexes of the Trications of Eu, Gd, and Tb.

All versions of our previous Sparkle Model were very accurate in predicting lanthanide-lanthanide distances in complexes where the two lanthanide ions directly face each other, and mainly lanthanide-oxygen, and lanthanide-nitrogen distances, which are by far the most common ones in lanthanide complexes. In this article, we are advancing for the first time the RM1 model for lanthanides. Designed to be a much more general NDDO model, the RM1 model for lanthanides is capable of predicting geometries of lanthanide complexes for the cases when the central lanthanide trication is directly coordinated to any other atoms, not only oxygen or nitrogen.

Semiempirical quantum chemistry model for the lanthanides: RM1 (Recife Model 1) parameters for dysprosium, holmium and erbium.

Complexes of dysprosium, holmium, and erbium find many applications as single-molecule magnets, as contrast agents for magnetic resonance imaging, as anti-cancer agents, in optical telecommunications, etc. Therefore, the development of tools that can be proven helpful to complex design is presently an active area of research. In this article, we advance a major improvement to the semiempirical description of lanthanide complexes: the Recife Model 1, RM1, model for the lanthanides, parameterized for the trications of Dy, Ho, and Er.

Sparkle/PM7 Lanthanide Parameters for the Modeling of Complexes and Materials.

The recently published Parametric Method number 7, PM7, is the first semiempirical method to be successfully tested by modeling crystal structures and heats of formation of solids. PM7 is thus also capable of producing results of useful accuracy for materials science, and constitutes a great improvement over its predecessor, PM6. In this article, we present Sparkle Model parameters to be used with PM7 that allow the prediction of geometries of metal complexes and materials which contain lanthanide trications.

Performance assessment of semiempirical molecular orbital methods in the structural prediction of Sb(III) and Bi(III) complexes.

In this paper we carried out a systematic study in order to assess the quality of some semiempirical methods (AM1, PM3 and PM6), comparing predicted structural properties of many Sb(III) and Bi(III) complexes with the corresponding experimental data, indicating which one is more appropriate to describe the structure of such compounds. Root-mean squared deviation (RMSD) and unsigned mean error (UME) were used to evaluate the accuracy of the semiempirical methods to predict the ground state geometries of complexes with many ligand types. Our results have shown that, in general, PM3 predicts more accurately the geometry of Sb(III) complexes, being considered by us as the method of choice to study Sb(III) complexes with a great variety of ligands.