Hydrodesulfurization of Dibenzothiophene: A Machine Learning Approach.

The hydrodesulfurization (HDS) process is widely used in the industry to eliminate sulfur compounds from fuels. However, removing dibenzothiophene (DBT) and its derivatives is a challenge. Here, the key aspects that affect the efficiency of catalysts in the HDS of DBT were investigated using machine learning (ML) algorithms. The conversion of DBT and selectivity was estimated by applying Lasso, Ridge, and Random Forest regression techniques. For the estimation of conversion of DBT, Random Forest and Lasso offer adequate predictions. At the same time, regularized regressions have similar outcomes, which are suitable for selectivity estimations. According to the regression coefficient, the structural parameters are essential predictors for selectivity, highlighting the pore size, and slab length. These properties can connect with aspects like the availability of active sites. The insights gained through ML techniques about the HDS catalysts agree with the interpretations of previous experimental reports.

Conformational preference of dipeptide zwitterions in aqueous solvents.

Proper description of solvent effects is challenging for theoretical methods, particularly if the solute is a zwitterion. Here, a series of theoretical procedures are used to determine the preferred solvated conformations of twelve hydrophobic dipeptides (Leu-Leu, Leu-Phe, Phe-Leu, Ile-Leu, Phe-Phe, Ala-Val, Val-Ala, Ala-Ile, Ile-Ala, Ile-Val, Val-Ile and Val-Val) in the zwitterionic state. First, the accuracy of density functional theory (DFT), combined with different implicit solvent models, for describing zwitterions in aqueous solvent is assessed by comparing the predicted against the experimental glycine tautomerization energy, i.e., the energetic difference between canonical and zwitterionic glycine in aqueous solvents. It is found that among the tested solvation schemes, the charge-asymmetric nonlocally determined local-electric solvation model (CANDLE) predicts an energetic difference in excellent agreement with the experimental value. Next, DFT-CANDLE is used to determine the most favorable solvated conformation for each of the investigated dipeptide zwitterions. The CANDLE-solvated structures are obtained by exploring the conformational space of each dipeptide zwitterion concatenating DFT calculations, in vacuum, with classical molecular dynamics simulations, in explicit solvents, and DFT calculations including explicit water molecules. It is found that the energetically most favorable conformations are similar to those of the dipeptide zwitterions in their respective crystal structures. Such structural agreement is indicative of the DFT-CANDLE accomplishment of the description of solvated zwitterions, and suggests that these biomolecules self-assemble as quasi-rigid objects.

Effect of strand register in the stability and reactivity of crystals from peptides forming amyloid fibrils.

Amyloids are cytotoxic protein aggregates that deposit in human tissues, leading to several health disorders. Their aggregates can also exhibit catalytic properties, and they have been used as candidates for the development of functional biomaterials. Despite being polymorphic, amyloids often assemble as cross-ß fibrils formed by in-register ß sheet layers. Recent studies of some amyloidogenic protein segments revealed that they crystallize as antiparallel out-of-register ß sheets. Such arrangement has been proposed to be responsible for the cytotoxicity in amyloid diseases, however, there is still no consensus on the molecular mechanism. Interestingly, two amyloidogenic peptide segments, NFGAILS and FGAILSS, arrange into out-of-register and in-register ß sheets, respectively, even though they solely differ by one aminoacid residue at both termini. In this work, we used density functional theory (DFT) to address how the strand register contributes into the packing and molecular properties of the NFGAILS and FGAILSS crystals. Our results show that the out-of-register structure is substantially more stable, at 0 K, than the in-register one due to stronger inter-strand contacts. Based on an analysis of the electrostatic potential of the crystal slabs, it is suggested that the out-of-register may potentially interact with negatively charged groups, like those found in cell membranes. Moreover, calculated reactivity descriptors indicate a similar outcome, where only the out-of-register peptide exhibits intrinsic reactive surface sites at the exposed amine and carboxylic groups. It is therefore suggested that the out-of-register arrangement may indeed be crucial for amyloid cytotoxicity. The findings presented here could help to further our understanding of amyloid aggregation, function, and toxicity.

Activated layered double hydroxides: assessing the surface anion basicity and its connection with the catalytic activity in the cyanoethylation of alcohols.

Layered double hydroxides (LDHs) act as catalysts in several reactions like in the cyanoethylation of alcohols with acrylonitrile to produce alkoxypropionitriles. Here we report an experimental and theoretical study in which it is shown that the experimental catalytic activity of LDHs in the cyanoethylation of 2-propanol and methanol correlates with the predicted strength of the basicity of the adsorbed surface species. First, it is shown that using activated LDHs containing Mg2+ and Al3+ (MgAl-LDH), Mg2+ and Ga3+ (MgGa-LDH), and Mg2+, Al3+ and Ga3+ (MgAlGa-LDH) great conversions to alkoxypropionitriles in high yields are obtained. Next, the basicity of these LDHs is estimated by means of the local softness, a local reactivity index calculated using density functional theory and appropriate surface models. For that, the adsorption of hydroxide and methoxide anions at the (001) surface of MgAl and MgGa-LDHs is investigated. We include LDHs containing Zn2+ and Al3+ (ZnAl-LDH) and Zn2+ and Ga3+ (ZnGa-LDH) in this part of the study to account for the effect of changing the divalent and trivalent metal composition on the basicity. It is found that hydroxide anions adsorbed on the MgGa-LDH surface and methoxide anions adsorbed on the MgAl-LDH surface are the most basic ones. This basicity trend correlates with our experimental findings about the catalytic activity of the activated LDHs. Further analyzing the connection between the LDH composition and the anion basicity, it is argued that the key steps dictating the LDH catalytic activity are the alcohol deprotonation in the cyanoethylation of 2-propanol, as it has been previously suggested, and the methoxide anion attack to the acrylonitrile double bond in the methanol cyanoethylation reaction.

Understanding the unusual stiffness of hydrophobic dipeptide crystals.

The hydrophobic diphenylalanine peptide crystal is known to be unusually stiff, with an experimental Young's modulus in the range of 19-27 GPa. Here it is shown by means of density functional theory calculations that phenylalanine-leucine, leucine-phenylalanine, alanine-valine, valine-alanine and valine-valine hydrophobic dipeptide crystals are also unusually stiff, with Young's moduli in the range of 19.7-33.3 GPa. To further our understanding of the origin of that unusual stiffness, a linear correlation is established between Young's modulus and the strength and orientation of the hydrogen bond network developed along the crystals, showing that stiffness in these materials is primarily dictated by hydrogen bonding.

PSIQUE: Protein Secondary Structure Identification on the Basis of Quaternions and Electronic Structure Calculations.

The secondary structure is important in protein structure analysis, classification, and modeling. We have developed a novel method for secondary structure assignment, termed PSIQUE, based on the potential energy surface (PES) of polyalanine obtained using an infinitely long chain model and density functional theory calculations. First, uniform protein segments are determined in terms of a difference of quaternions between neighboring amino acids along the protein backbone. Then, the identification of the secondary structure motifs is carried out based on the minima found in the PES. PSIQUE shows good agreement with other secondary structure assignment methods. However, it provides better discrimination of subtle secondary structures (e.g., helix types) and termini and produces more uniform segments while also accounting for local distortions. Overall, PSIQUE provides a precise and reliable assignment of secondary structures, so it should be helpful for the detailed characterization of the protein structure.

Hydrogen bonding capabilities of group 14 homologues of HCN and HNC.

This study is directed towards assessing hydrogen bond acceptor/donor capabilities of heavier group 14 homologues of HCN and HNC. A structural, energetic and topological study using ab initio (MP2, CCSD(T)), electrostatic potential (EP) and quantum theory of atoms in molecules (QTAIM) methodologies was carried out on HNX⋯HNX and HXN⋯HXN dimers and their respective monomers, where X = C, Si, Ge, Sn and Pb. The obtained results suggest the presence of weak hydrogen bonds in both kinds of complexes, and remarkably Ge and Sn act as unconventional hydrogen donors.

Modeling cooperative effects in halogen-bonded infinite linear chains.

Non-additivity in noncovalent interactions is an important aspect of complex systems that can lead to stronger (cooperative) interactions when three or more molecular units influence each other. The halogen bond (XB) is a highly-directional noncovalent interaction that has been found to be cooperative. Here the strength and nature of cooperativity arising in X-bonded infinite linear chains of cyanogen halides and 4-halopyridines are investigated by means of density functional theory calculations. It is found that cyanogen halide chains are highly cooperative (up to 77%), whereas pyridines are only slightly cooperative (below 21%). It is demonstrated that XB and its non-additivity can be modeled as the sum of a local term, which depends on first nearest-neighbors only, and long-range effective dipole-dipole attractions. It is shown that the local term in cyanogen halides primarily accounts for repulsive short-range screened Coulomb interactions, whereas in 4-halopyridines such a term also includes attractive contributions, which are particularly sizeable in some elongated XB conformations. This outcome reveals differences in the nature of the XBs formed in these molecular systems. Nevertheless, it is shown that both systems behave as effective point dipoles regarding cooperative effects, at any point of the XB dissociation path. As such, these results are useful contributions for the understanding and modeling of non-additive effects of noncovalent interactions.

Origin of cooperativity in hydrogen bonding.

The origin of non-additivity in hydrogen bonds (H-bonds), usually termed as H-bond cooperativity, is investigated in H-bonded linear chains. It is shown that H-bond cooperativity originates solely from classical electrostatics. The latter is corroborated by comparing the H-bond cooperativity in infinitely-long H-bonded hydrogen cyanide, 4-pyridone and formamide chains, assessed using density functional theory (DFT), against the strengthening of the dipole-dipole interaction upon the formation of an infinite chain of effective point-dipoles. It is found that the magnitude of these effective point-dipoles is a consequence of mutual polarization and additional effects beyond a polarizable point-dipole model. Nevertheless, the effective point-dipoles are fully determined once a single H-bond is formed, indicating that quantum effects involved in H-bonding are circumscribed to nearest-neighbor interactions only; i.e. in a linear chain of H-bonds, quantum effects do not contribute to the H-bond non-additivity. This finding is verified by estimating cooperativity along the dissociation path of H-bonds in the infinite chains, using two empirical parameters that account for polarizability, together with DFT association energies and molecular dipoles of solely monomers and dimers.

On cooperative effects and aggregation of GNNQQNY and NNQQNY peptides.

Some health disturbances like neurodegenerative diseases are associated to the presence of amyloids. GNNQQNY and NNQQNY peptides are considered as prototypical examples for studying the formation of amyloids. These exhibit quite different aggregation behaviors despite they solely differ in size by one residue. To get insight into the reasons for such difference, we have examined association energies of aggregates (parallel ß-sheets, fibril-spines, and crystal structures) from GNNQQNY and NNQQY using density functional theory. As we found that GNNQQNY tends to form a zwitterion in the crystal structure, we have investigated the energetics of parallel ß-sheets and fibril-spines in the canonical and zwitterionic states. We found that the formation of GNNQQNY aggregates is energetically more favored than the formation of the NNQQNY ones. We show that the latter is connected to the network of hydrogen bonds formed by each aggregate. Moreover, we found that the formation of some NNQQNY aggregates is anticooperative, whereas cooperative with GNNQQNY. These results have interesting implications for deciphering the factors determining peptide aggregation propensities.

Theoretical investigations on the layer-anion interaction in Mg-Al layered double hydroxides: influence of the anion nature and layer composition.

The influence of the anion nature and layer composition on the anion-layer interaction in Mg-Al layered double hydroxides (LDHs) is investigated using density functional theory. Changes in the strength of the anion-layer interaction are assessed calculating the potential energy surface (PES) associated to the interlayer anion (OH(-)/Cl(-)) in Mg-Al-OH and Mg-Al-Cl LDHs. The layer composition is varied changing the divalent to trivalent cation proportion (R). Mg-Al-OH is thus investigated with R = 2, 3, 3.5 and Mg-Al-Cl with R = 3. It is found that the PES for OH(-) in Mg-Al-OH/R = 3 presents wider energy basins and lower energy barriers than any other of the investigated compositions. It is shown that the latter is connected to the number of hydrogen bonds formed by the anions. These results have interesting implications for understanding the enhancement of the physicochemical properties of LDHs upon changing composition.

Sensing polarization effects through the analysis of the effective C6 dispersion coefficients in NaCl solutions.

Density functional theory based ab initio molecular dynamics is used to obtain microscopic details of the interactions in sodium chloride solutions. By following the changes in the atomic C6 coefficients under the Tkatchenko-Scheffler's scheme, we were able to identify two different coordination situations for the Cl(-) ion with significant different capabilities to perform dispersion interactions. This capability is enhanced when the ion-ion distance corresponds to the contact ion-pair situation. Also, the oxygen and hydrogen atoms of the water molecules change their aptitudes to interact through van der Waals like terms when they are close to the cation region of the ion-pair. These results have interesting implications on the design of force fields to model electrolyte solutions.

A density functional theory based estimation of the anharmonic contributions to the free energy of a polypeptide helix.

We have employed density functional theory to determine the temperature dependence of the intrinsic stability of an infinite poly-L-alanine helix. The most relevant helix types, i.e., the α- and the 3(10)-helix, and several unfolded conformations, which serve as reference for the stability analysis, have been included. For the calculation of the free energies for the various chain conformations we have explicitly included both, harmonic and anharmonic contributions. The latter have been calculated by means of a thermodynamic integration approach employing stochastic Langevin molecular dynamics, which is shown to provide a dramatic increase in the computational efficiency as compared to commonly employed deterministic molecular dynamics schemes. Employing this approach we demonstrate that the anharmonic part of the free energy amounts to the order of 0.1-0.4 kcal/mol per peptide unit for all analysed conformations. Although small, the anharmonic contribution stabilizes the helical conformations with respect to the fully extended structure.

Unraveling the stability of polypeptide helices: critical role of van der Waals interactions.

Folding and unfolding processes are important for the functional capability of polypeptides and proteins. In contrast with a physiological environment (solvated or condensed phases), an in vacuo study provides well-defined "clean room" conditions to analyze the intramolecular interactions that largely control the structure, stability, and folding or unfolding dynamics. Here we show that a proper consideration of van der Waals (vdW) dispersion forces in density-functional theory (DFT) is essential, and a recently developed DFT+vdW approach enables long time-scale ab initio molecular dynamics simulations at an accuracy close to "gold standard" quantum-chemical calculations. The results show that the inclusion of vdW interactions qualitatively changes the conformational landscape of alanine polypeptides, and greatly enhances the thermal stability of helical structures, in agreement with gas-phase experiments.

Microsolvation Effect on the Twist of ß-sheets.

Under certain circumstances ß-sheets prefer to be twisted instead of flat. To get insight into the reasons of such preference, bare and microsolvated parallel and antiparallel two-strand polyalanine ß-sheets are investigated using density functional theory. Full geometry optimizations show that microsolvation increases interstrand twisting and promotes a flat to twist transition. It is found that the latter behavior is connected to compressive strain resulting from microsolvation. Residues in flat ß-sheets adjust the sense of its local intrastrand twist, which leads to the appearance of interstrand twist, to release strain and to favor water-water hydrogen bonding. The predicted microsolvation effect is corroborated analyzing the geometry of residues forming ß-sheet motifs in protein crystals.

Density functional theory study of the conformational space of an infinitely long polypeptide chain.

The backbone conformational space of infinitely long polyalanine is investigated with density-functional theory and mapping the potential energy surface in terms of (L, theta) cylindrical coordinates. A comparison of the obtained (L, theta) Ramachandran-like plot with results from an extended set of protein structures shows excellent conformity, with the exception of the polyproline II region. It is demonstrated the usefulness of infinitely long polypeptide models for investigating the influence of hydrogen bonding and its cooperative effect on the backbone conformations. The results imply that hydrogen bonding together with long-range electrostatics is the main actuator for most of the structures assumed by protein residues.

Energetics of infinite homopolypeptide chains: a new look at commonly used force fields.

We present a novel method for comparing the long-range part of force fields in the presence of a maximally cooperative network of nonbonded interactions. The method is based on mapping the potential energy surface of an infinite polypeptide chain in the gas phase by using cylindrical coordinates (the twist and pitch) as geometry descriptors. We apply our method to an infinite polyalanine chain and consider the AMBER99, AMBER99SB, CHARMM27, and OPLS-AA/L fixed partial-charge force fields and the protein-specific version of the AMOEBA polarizable force field. Results from our analysis are compared to those obtained from high-level density-functional theory (DFT) calculations. We find that all force fields produce stronger stabilization of the helical conformations as compared to DFT, with only AMBER99/AMBER99SB satisfactorily reproducing all three helical conformations (pi, alpha, and 3(10)).

First-principles free-energy analysis of helix stability: the origin of the low entropy in pi helices.

The temperature dependence of the stability of infinite poly-L-alanine alpha, pi, and 310 helices with respect to the fully extended structure (FES) is calculated using density functional theory and the harmonic approximation. We find that the vibrational entropy strongly reduces the stability of the helical conformations with respect to the FES. By mapping the ab initio data on an approximate mechanical model, we show that this effect is exclusively due to the formation of hydrogen bonds, whereas changes in the backbone stiffness are practically negligible. We furthermore observe that the temperature dependence is largest for the pi helix and smallest for the 310 helix and demonstrate that these trends are a generic behavior related to the geometric peculiarities of the respective helical conformations and independent of the specific amino acid sequence.

Theoretical investigations of oxygen-17 NMR chemical shifts to discriminate among helical forms.

17O, 15N, 13C, and 1H NMR chemical shieldings are calculated using density functional theory to differentiate among the three primarily helical forms, 310, alpha, and pi in polyalanine peptides under periodic boundary conditions. This study suggests 17O as the best observable, as it has been demonstrated to be sensitive to hydrogen bonding and highly affected by small changes in the polypeptide in helix conformations. This theoretical study seeks to characterize the subtle conformational differences of helical structures by NMR chemical shift observables which may lead to important questions in experimental structure determination on the basis of using chemical shifts to identify protein secondary structures.

Structural transitions in the polyalanine alpha-helix under uniaxial strain.

We analyzed the response to strain of an infinite polyalanine chain in the alpha-helical conformation using density functional theory. Under compressive strain the alpha-helix is found to undergo structural transitions to a pi-helix when the length of the helix is reduced by more than 10%. Under tensile strain the structure changes into a 3(10)-helix when the length is stretched by more than 10%. Our analysis of these transitions shows that they proceed essentially in two steps: At first there is mainly a length change, and only with some delay the helix twist adjusts.