José R. B. Gomes

Effect of the exchange-correlation potential and of surface relaxation on the description of the H2O dissociation on Cu(111)

The role of the exchange-correlation density functional (PBE, PW91, RevPBE) and of surface relaxation in the determination of the adsorption energies, reaction energy barriers, and reaction rate constants has been analyzed taking water dissociation on Cu(111) surface as a test case. The PBE and PW91 functionals yield similar adsorption geometries and, adsorption and activation energies, but differ significantly from RevPBE results. For each of the functionals tested, surface relaxation was found to have only a minor effect on the calculated (co)adsorption geometries and (co)adsorption energies. The calculated energy barriers for water dissociation are more affected by the functional used, especially in the case of the RevPBE, with obvious implications on the calculated energy barriers and derived reaction rate constants.

Accounting for van der Waals interactions between adsorbates and surfaces in density functional theory based calculations: selected examples

This article reviews the different density functional theory (DFT) methods available in the literature for dealing with dispersion interactions and recent applications of DFT approaches including van der Waals corrections in the study of the interaction of atoms and molecules with several different surfaces. Focus is given to the interaction of atoms and molecules with metal, metal oxide and graphite surfaces or more complex systems. It will be shown that DFT approaches including van der Waals corrections present significant advances over standard exchange–correlation functionals for treating systems dominated by weak interactions.

Good performance of the M06 family of hybrid meta generalized gradient approximation density functionals on a difficult case: CO adsorption on MgO(001)

The adsorption of CO on Mg(001) constitutes a challenge for current density functional approximations because of its weak interaction character. In the present work we show that the M06-2X and M06-HF exchange-correlation functionals are the first ones to provide a simultaneously satisfactory description of adsorbate geometry, vibrational frequency shift, and adsorption energy of CO on MgO(001). For a sufficiently large embedded cluster model, the three functionals of the M06 family-which contain a nonzero percentage of Hartree-Fock exchange (M06, M06-2X, and M06-HF)-all predict positive C-O vibrational shifts, in agreement with the experimental findings, while the local M06-L functional gives large negative shifts. Moreover, the shifts computed with the M06-2X and M06-HF potentials are in good agreement with the experimental shift of +14 cm(-1). The interaction energy (D(e)) calculated with M06-2X and M06-HF is approximately 6.0 kcal/mol, which agrees well with the D(e) value ( approximately 4 kcal/mol) deduced from the D(0) obtained in thermal desorption measurements on single-crystal surfaces.

Salting-in with a Salting-out Agent: Explaining the Cation Specific Effects on the Aqueous Solubility of Amino Acids

Although the understanding of ion specific effects on the aqueous solubilities of biomolecules is crucial for the development of many areas of biochemistry and life sciences, a consensual and well-supported molecular picture of the phenomena has not yet been established. Mostly, the influence of cations and the nature of the molecular interactions responsible for the reversal of the Hofmeister trend in aqueous solutions of amino acids and proteins are still defectively understood. Aiming at contributing to the understanding of the molecular-level mechanisms governing the cation specific effects on the aqueous solubilities of biocompounds, experimental solubility measurements and classical molecular dynamics simulations were performed for aqueous solutions of three amino acids (alanine, valine, and isoleucine), in the presence of a series of inorganic salts. The evidence gathered suggests that the mechanism by which salting-in inducing cations operate in aqueous solutions of amino acids is different from that of anions, and allows for a novel and consistent molecular description of the effect of the cation on the solubility based on specific interactions of the cations with the negatively charged moieties of the biomolecules.

Viral surface glycoproteins, gp120 and gp41, as potential drug targets against HIV-1: Brief overview one quarter of a century past the approval of zidovudine, the first anti-retroviral drug

The first anti-HIV drug, zidovudine (AZT), was approved by the FDA a quarter of a century ago, in 1985. Currently, anti-HIV drug-combination therapies only target HIV-1 protease and reverse transcriptase. Unfortunately, most of these molecules present numerous shortcomings such as viral resistances and adverse effects. In addition, these drugs are involved in later stages of infection. Thus, it is necessary to develop new drugs that are able to block the first steps of viral life cycle. Entry of HIV-1 is mediated by its two envelope glycoproteins: gp120 and gp41. Upon gp120 binding to cellular receptors, gp41 undergoes a series of conformational changes from a non-fusogenic to a fusogenic conformation. The fusogenic core of gp41 is a trimer-of-hairpins structure in which three C-terminal helices pack against a central trimeric-coiled coil formed by three N-terminal helices. The formation of this fusogenic structure brings the viral and cellular membranes close together, a necessary condition for membrane fusion to occur. As gp120 and gp41 are attractive targets, the development of entry inhibitors represents an important avenue of anti-HIV drug therapy. The present review will focus on some general considerations about HIV, the main characteristics of gp120, gp41 and their inhibitors, with special emphasis on the advances of computational approaches employed in the development of bioactive compounds against HIV-1 entry process.

Falcipains, Plasmodium falciparum Cysteine Proteases as Key Drug Targets Against Malaria

There is a high demand for new drugs against malaria, which takes millions of lives annually. The abuse of classical antimalarials from the late 1940s to the early 1980s has bred resistant parasites, which led to the use of more potent drugs that ended up by refueling the resistance cycle. An example is chloroquine, once highly effective but now virtually useless against malaria. Structure-based rational drug design relies on high-resolution target structures to allow for screening of selective ligands/inhibitors. For the past two decades, and especially after the unveiling of the Plasmodium falciparum genome in 2002, enzymes of this lethal malaria parasite species have been increasingly attracting the attention of Medicinal Chemists worldwide as promising drug targets. There is particular emphasis on proteases having key roles on the degradation of hosts hemoglobin within the food vacuole of blood-stage parasites, as these depend on such process for their survival. Among such enzymes, Plasmepsins (aspartic proteases) and, especially, Falcipains (cysteine proteases) are highly promising antimalarial drug targets. The present review will focus on the computational approaches made so far towards the unraveling of the structure, function and inhibition of Falcipains that, by virtue of their quite specific features, are excellent targets for highly selective inhibitors.

Molecular Dynamics Simulation Studies of the Interactions between Ionic Liquids and Amino Acids in Aqueous Solution

Although the understanding of the influence of ionic liquids (ILs) on the solubility behavior of biomolecules in aqueous solutions is relevant for the design and optimization of novel biotechnological processes, the underlying molecular-level mechanisms are not yet consensual or clearly elucidated. In order to contribute to the understanding of the molecular interactions established between amino acids and ILs in aqueous media, classical molecular dynamics (MD) simulations were performed for aqueous solutions of five amino acids with different structural characteristics (glycine, alanine, valine, isoleucine, and glutamic acid) in the presence of 1-butyl-3-methylimidazolium bis(trifluoromethyl)sulfonyl imide. The results from MD simulations enable to relate the properties of the amino acids, namely their hydrophobicity, to the type and strength of their interactions with ILs in aqueous solutions and provide an explanation for the direction and magnitude of the solubility phenomena observed in [IL + amino acid + water] systems by a mechanism governed by a balance between competitive interactions of the IL cation, IL anion, and water with the amino acids.

Modeling Adsorption in Metal–Organic Frameworks with Open Metal Sites: Propane/Propylene Separations

We present a new approach for modeling adsorption in metal-organic frameworks (MOFs) with unsaturated metal centers and apply it to the challenging propane/propylene separation in copper(II) benzene-1,3,5-tricarboxylate (CuBTC). We obtain information about the specific interactions between olefins and the open metal sites of the MOF using quantum mechanical density functional theory. A proper consideration of all the relevant contributions to the adsorption energy enables us to extract the component that is due to specific attractive interactions between the π-orbitals of the alkene and the coordinatively unsaturated metal. This component is fitted using a combination of a Morse potential and a power law function and is then included into classical grand canonical Monte Carlo simulations of adsorption. Using this modified potential model, together with a standard Lennard-Jones model, we are able to predict the adsorption of not only propane (where no specific interactions are present), but also of propylene (where specific interactions are dominant). Binary adsorption isotherms for this mixture are in reasonable agreement with ideal adsorbed solution theory predictions. We compare our approach with previous attempts to predict adsorption in MOFs with open metal sites and suggest possible future routes for improving our model.

Density functional study of CO and NO adsorption on Ni-doped MgO(100)

The adsorption of small molecules such as NO or CO on surfaces of magnetic oxides containing transition metals is difficult to model by current density functional approximations. Two such oxides are NiO(100) and Ni-doped MgO(100). Here we compare the results of a theoretical model of the Ni-doped MgO(100) surface with experimental results on NiO(100), which introduces some uncertainty into a quantitative theory-experiment comparison. In the present work, we tested seven meta-GGA and hybrid metafunctionals, in particular, three developed by the Minnesota group (M05, M06-L, and M06), and TPSS, TPSSh, TPSSKCIS, and B1B95; six GGA functionals, including BP86, PBE, and four other functionals that are modifications of PBE (PBEsol, SOGGA, revPBE, and RPBE); five hybrid GGA functionals (B3LYP, PBE0, B97-2, B97-3, and MPWLYP1M); and one unconventional functional of the generalized gradient type with scaled correlation called MOHLYP. The Minnesota meta-GGA functionals were found in the past to be very good choices when transition metal atoms were present; the other functionals chosen are a selection from the most currently used and most promising sets of functionals for bulk solids and surfaces and for transition metals. The difficulty is due to the charge transfer between open shells in the case of NO and to the weak character of the interaction in the case of CO. It is shown that the M06 hybrid meta functional applied to NO or CO on a model of the Ni-doped MgO(100) surface is able to provide a good description of both adsorbate geometries and binding energies. The M06 vibrational frequency shifts are more accurate than for other functionals, but there is still room for improvement.

Surface model and exchange-correlation functional effects on the description of Pd/α-Al2O3(0001)

The interaction of Pd with the Al-terminated α-Al2O3(0001) surface has been investigated using an embedded cluster model and periodic-supercell approaches. Furthermore, several treatments of electronic exchange and correlation within density functional (DF) theory have been employed including generalized gradient approximation (GGA) and hybrid exchange functionals. In the periodic calculations the influence of pseudopotentials and basis sets have also been investigated by comparing GGA results obtained using all electron basis set and pseudopotential plane-wave approaches. For a given choice of the exchange-correlation functional and for a fixed substrate, the cluster and slab models predict nearly the same structural parameters and adsorption energies. All structural models reproduce the general trend for the interaction of Pd with the α-Al2O3(0001) surface, which is that there is a slight preference for adsorption above surface sites sitting directly above oxygen atoms either from the second or fifth la...