Twenty years ago, the landmark AM1 was introduced, and has since had an increasingly wide following among chemists due to its consistently good results and time-tested reliability--being presently available in countless computational quantum chemistry programs. However, semiempirical molecular orbital models still are of limited accuracy and need to be improved if the full potential of new linear scaling techniques, such as MOZYME and LocalSCF, is to be realized. Accordingly, in this article we present RM1 (Recife Model 1): a reparameterization of AM1. As before, the properties used in the parameterization procedure were: heats of formation, dipole moments, ionization potentials and geometric variables (bond lengths and angles). Considering that the vast majority of molecules of importance to life can be assembled by using only six elements: C, H, N, O, P, and S, and that by adding the halogens we can now build most molecules of importance to pharmaceutical research, our training set consisted of 1736 molecules, representative of organic and biochemistry, containing C, H, N, O, P, S, F, Cl, Br, and I atoms. Unlike AM1, and similar to PM3, all RM1 parameters have been optimized. For enthalpies of formation, dipole moments, ionization potentials, and interatomic distances, the average errors in RM1, for the 1736 molecules, are less than those for AM1, PM3, and PM5. Indeed, the average errors in kcal x mol(-1) of the enthalpies of formation for AM1, PM3, and PM5 are 11.15, 7.98, and 6.03, whereas for RM1 this value is 5.77. The errors, in Debye, of the dipole moments for AM1, PM3, PM5, and RM1 are, respectively, 0.37, 0.38, 0.50, and 0.34. Likewise, the respective errors for the ionization potentials, in eV, are 0.60, 0.55, 0.48, and 0.45, and the respective errors, in angstroms, for the interatomic distances are 0.036, 0.029, 0.037, and 0.027. The RM1 average error in bond angles of 6.82 degrees is only slightly higher than the AM1 figure of 5.88 degrees, and both are much smaller than the PM3 and PM5 figures of 6.98 degrees and 9.83 degrees, respectively. Moreover, a known error in PM3 nitrogen charges is corrected in RM1. Therefore, RM1 represents an improvement over AM1 and its similar successor PM3, and is probably very competitive with PM5, which is a somewhat different model, and not fully disclosed. RM1 possesses the same analytical construct and the same number of parameters for each atom as AM1, and, therefore, can be easily implemented in any software that already has AM1, not requiring any change in any line of code, with the sole exception of the values of the parameters themselves.

Our previously defined Sparkle model (Inorg. Chem. 2004, 43, 2346) has been reparameterized for Eu(III) as well as newly parameterized for Gd(III) and Tb(III). The parameterizations have been carried out in a much more extensive manner, aimed at producing a new, more accurate model called Sparkle/AM1, mainly for the vast majority of all Eu(III), Gd(III), and Tb(III) complexes, which possess oxygen or nitrogen as coordinating atoms. All such complexes, which comprise 80% of all geometries present in the Cambridge Structural Database for each of the three ions, were classified into seven groups. These were regarded as a "basis" of chemical ambiance around a lanthanide, which could span the various types of ligand environments the lanthanide ion could be subjected to in any arbitrary complex where the lanthanide ion is coordinated to nitrogen or oxygen atoms. From these seven groups, 15 complexes were selected, which were defined as the parameterization set and then were used with a numerical multidimensional nonlinear optimization to find the best parameter set for reproducing chemical properties. The new parameterizations yielded an unsigned mean error for all interatomic distances between the Eu(III) ion and the ligand atoms of the first sphere of coordination (for the 96 complexes considered in the present paper) of 0.09 A, an improvement over the value of 0.28 A for the previous model and the value of 0.68 A for the first model (Chem. Phys. Lett. 1994, 227, 349). Similar accuracies have been achieved for Gd(III) (0.07 A, 70 complexes) and Tb(III) (0.07 A, 42 complexes). Qualitative improvements have been obtained as well; nitrates now coordinate correctly as bidentate ligands. The results, therefore, indicate that Eu(III), Gd(III), and Tb(III) Sparkle/AM1 calculations possess geometry prediction accuracies for lanthanide complexes with oxygen or nitrogen atoms in the coordination polyhedron that are competitive with present day ab initio/effective core potential calculations, while being hundreds of times faster.

Applications of hybrid QM/MM methods range from reactions in active sites of small enzymes to multiple sites in large bioenergetic complexes. By combining the widely used molecular dynamics and visualization programs NAMD/VMD with the quantum chemistry packages ORCA, and MOPAC, we provide an integrated, comprehensive, customizable, and easy-to-use suite. Through the QwikMD interface, setup, execution, visualization, and analysis are streamlined for all levels of expertise.

In this study, we present some modifications in the semiempirical quantum chemistry MOPAC2009 code that accelerate single-point energy calculations (1SCF) of medium-size (up to 2500 atoms) molecular systems using GPU coprocessors and multithreaded shared-memory CPUs. Our modifications consisted of using a combination of highly optimized linear algebra libraries for both CPU (LAPACK and BLAS from Intel MKL) and GPU (MAGMA and CUBLAS) to hasten time-consuming parts of MOPAC such as the pseudodiagonalization, full diagonalization, and density matrix assembling. We have shown that it is possible to obtain large speedups just by using CPU serial linear algebra libraries in the MOPAC code. As a special case, we show a speedup of up to 14 times for a methanol simulation box containing 2400 atoms and 4800 basis functions, with even greater gains in performance when using multithreaded CPUs (2.1 times in relation to the single-threaded CPU code using linear algebra libraries) and GPUs (3.8 times). This degree of acceleration opens new perspectives for modeling larger structures which appear in inorganic chemistry (such as zeolites and MOFs), biochemistry (such as polysaccharides, small proteins, and DNA fragments), and materials science (such as nanotubes and fullerenes). In addition, we believe that this parallel (GPU-GPU) MOPAC code will make it feasible to use semiempirical methods in lengthy molecular simulations using both hybrid QM/MM and QM/QM potentials.

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 54.3 and 43.0 degrees, respectively. The RBD region was more exposed to the solvent and to the possible drugs due to its enhanced surface area. From the equilibrated MD structure, virtual screening by docking calculations were performed using a library contained 9091 FDA approved drugs. Among them, 24 best-scored ligands (14 traditional herbal isolate and 10 approved drugs) with the binding energy below -8.1 kcal/mol were selected as potential candidates to inhibit the SARS-CoV-2 S-protein, preventing the human cell infection and their replication. For instance, the ivermectin drug (present in our list of promise candidates) was recently used successful to control viral replication in vitro. MD simulations were performed for the three best ligands@S-protein complexes and the binding energies were calculated using the MM/ PBSA approach. Overall, it is highlighted an important strategy, some key residues, and chemical groups which may be considered on clinical trials for COVID-19 outbreak.

In the present work, we sought to improve our sparkle model for the calculation of lanthanide complexes, SMLC,in various ways: (i) inclusion of the europium atomic mass, (ii) reparametrization of the model within AM1 from a new response function including all distances of the coordination polyhedron for tris(acetylacetonate)(1,10-phenanthroline) europium(III), (iii) implementation of the model in the software package MOPAC93r2, and (iv) inclusion of spherical Gaussian functions in the expression which computes the core-core repulsion energy. The parametrization results indicate that SMLC II is superior to the previous version of the model because Gaussian functions proved essential if one requires a better description of the geometries of the complexes. In order to validate our parametrization, we carried out calculations on 96 europium(III) complexes, selected from Cambridge Structural Database 2003, and compared our predicted ground state geometries with the experimental ones. Our results show that this new parametrization of the SMLC model, with the inclusion of spherical Gaussian functions in the core-core repulsion energy, is better capable of predicting the Eu-ligand distances than the previous version. The unsigned mean error for all interatomic distances Eu-L, in all 96 complexes, which, for the original SMLC is 0.3564 A, is lowered to 0.1993 A when the model was parametrized with the inclusion of two Gaussian functions. Our results also indicate that this model is more applicable to europium complexes with beta-diketone ligands. As such, we conclude that this improved model can be considered a powerful tool for the study of lanthanide complexes and their applications, such as the modeling of light conversion molecular devices.

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. Accordingly, we considered the geometries of 224 high-quality crystallographic structures of complexes for the parameterization set and 395 more for the validation of the parameterization for the whole lanthanide series, from La(III) to Lu(III). The average unsigned error for Sparkle/PM7 for the distances between the metal ion and its coordinating atoms is 0.063Å for all lanthanides, ranging from a minimum of 0.052Å for Tb(III) to 0.088Å for Ce(III), comparable to the equivalent errors in the distances predicted by PM7 for other metals. These distance deviations follow a gamma distribution within a 95% level of confidence, signifying that they appear to be random around a mean, confirming that Sparkle/PM7 is a well-tempered method. We conclude by carrying out a Sparkle/PM7 full geometry optimization of two spatial groups of the same thulium-containing metal organic framework, with unit cells accommodating 376 atoms, of which 16 are Tm(III) cations; the optimized geometries were in good agreement with the crystallographic ones. These results emphasize the capability of the use of the Sparkle Model for the prediction of geometries of compounds containing lanthanide trications within the PM7 semiempirical model, as well as the usefulness of such semiempirical calculations for materials modeling. Sparkle/PM7 is available in the software package MOPAC2012, at no cost for academics and can be obtained from http://openmopac.net.

O modelo Sparkle/PM3 é parametrizado para complexos de európio (III), gadolínio (III) e térbio (III). A validação do modelo foi realizada utilizando noventa e seis complexos de Eu(III), setenta complexos de Gd(III) e quarenta e dois complexos de Tb(III); todos a partir de estruturas cristalográficas de alta qualidade, com fator R < 5%. Os erros médios absolutos, obtidos com o modelo Sparkle/PM3, considerando todas as distâncias interatômicas do tipo lantanídeo-átomo ligante, foram 0,080 Å para Eu(III), 0,063 Å para Gd(III) e 0,070 Å para Tb(III). Estes valores médios são similares aos obtidos com o modelo Sparkle/AM1 (0,082 Å, 0,061 Å, e 0,068 Å, respectivamente). Além disso, a exatidão em reproduzir o poliedro de coordenação de complexos de Eu(III), Gd(III) e Tb(III) é similar à obtida utilizando métodos ab initio com potenciais efetivos de caroço. Finalmente, com o objetivo de avaliar se as geometrias preditas com o modelo Sparkle/PM3 são confiáveis, escolhemos um dos complexos de Eu(III), BAFZEO, para o qual geramos centenas de diferentes geometrias iniciais, onde variamos de forma aleatória as distâncias e ângulos entre os ligantes e o íon Eu(III). Em seguida, todas essas geometrias iniciais foram otimizadas usando o modelo Sparkle/PM3. Como resultado, observamos uma tendência significativa onde a geometria que apresentou o menor erro médio absoluto apresentou também a energia total mais baixa, o que reforça a validade do modelo Sparkle.The Sparkle/PM3 model is extended to europium(III), gadolinium(III), and terbium(III) complexes. The validation procedure was carried out using only high quality crystallographic structures, for a total of ninety-six Eu(III) complexes, seventy Gd(III) complexes, and forty-two Tb(III) complexes. The Sparkle/PM3 unsigned mean error, for all interatomic distances between the trivalent lanthanide ion and the ligand atoms of the first sphere of coordination, is: 0.080 Å for Eu(III); 0.063 Å for Gd(III); and 0.070 Å for Tb(III). These figures are similar to the Sparkle/AM1 ones of 0.082 Å, 0.061 Å, and 0.068 Å respectively, indicating they are all comparable parameterizations. Moreover, their accuracy is similar to what can be obtained by present-day ab initio effective core potential full geometry optimization calculations on such lanthanide complexes. Finally, we report a preliminary attempt to show that Sparkle/PM3 geometry predictions are reliable. For one of the Eu(III) complexes, BAFZEO, we created hundreds of different input geometries by randomly varying the distances and angles of the ligands to the central Eu(III) ion, which were all subsequently fully optimized. A significant trend was unveiled, indicating that more accurate local minima geometries cluster at lower total energies, thus reinforcing the validity of sparkle model calculations. Keywords:Sparkle model, AM1, PM3, lanthanide complexes, rare earth coordination compounds IntroductionLanthanide complexes of the trivalent ions of europium, gadolinium, and terbium display a wide range of applications, with newer one...