Steven R. Gwaltney

Second-order correction to perfect pairing: an inexpensive electronic structure method for the treatment of strong electron-electron correlations.

We have formulated a second-order perturbative correction for perfect-pairing wave functions [PP2] based on similarity-transformed perturbation techniques in coupled cluster theory. The perfect-pairing approximation is used to obtain a simple reference wave function which can qualitatively describe bond breaking, diradicals, and other highly correlated systems, and the perturbative correction accounts for the dynamical correlation. An efficient implementation of this correction using the resolution of the identity approximation enables PP2 to be computed at a cost only a few times larger than that of canonical MP2 for systems with hundreds of active electrons and tens of heavy atoms. PP2 significantly improves on MP2 predictions in various systems with a challenging electronic structure.

Evaluation of the ‘side door’ in carboxylesterase-mediated catalysis and inhibition

Abstract Structures of mammalian carboxylesterases (CEs) reveal the presence of a ‘side door’ that is proposed to act as an alternative pore for the trafficking of substrates and products. p-Nitrobenzyl esterase (pnb CE) from Bacillus subtilis exhibits close structural homology and a similar side-door domain as mammalian CEs. We investigated the role of a specific ‘gate’ residue at the side door (i.e., Leu 362) during pnb CE-catalyzed hydrolysis of model esters, pesticides, and lipids. Recombinant pnb CE proteins containing mutations at position 362 demonstrated markedly lower k cat and k cat/K m values. The mutation with the most significant impact on catalysis was the L362R mutant (k cat/K m was 22-fold lower). Moreover, the ability of the L362R mutant to be inhibited by organophosphates (OP) was also lower. Investigation into the altered catalytic proficiency using pH-activity studies indicated that the catalytic triad of the mutant enzyme was preserved. Furthermore, viscosity variation and carbamate inhibition experiments indicated that rates of substrate association and acylation/deacylation were lower. Finally, recombinant CEs were found to possess lipolytic activity toward cholesteryl oleate and 2-arachidonylglycerol. In summary, the L362R mutant CE markedly slowed the rate of ester hydrolysis and was less sensitive to OP inhibition. The apparent causes of the diminished catalysis are discussed.

Approaching closed-shell accuracy for radicals using coupled cluster theory with perturbative triple substitutions

The erratic performance of CCSD(T) for radicals is analyzed using non-Hartree–Fock references as a starting point for correlations and by testing the (2) approach as an alternative to (T) for including higher-order correlation effects. Though CCSD(2) improves upon CCSD(T), correlating from a better-behaved reference makes both theories robust. Comparisons of calculated harmonic frequencies against experiment in a set of diatomic radicals from Brueckner-like orbitals demonstrate improvement approaching closed-shell accuracy. Additionally, we find that using BLYP Kohn–Sham orbitals yields similar improvements, and they are therefore a useful, inexpensive reference for high-level correlation methods in difficult systems. Root-mean-square errors of 1.0–1.2% are found in the cc-pVQZ basis for predicted harmonic frequencies in the test set using OD(T) and KS-CCSD(T), making these approaches quite competitive with CCSD(T) for closed-shell molecules. Finally, these improvements are correlated with spin contamination and the rate of change of the electron density with nuclear displacement.

An interatomic potential for saturated hydrocarbons based on the modified embedded-atom method

In this work, we developed an interatomic potential for saturated hydrocarbons using the modified embedded-atom method (MEAM), a reactive semi-empirical many-body potential based on density functional theory and pair potentials. We parameterized the potential by fitting to a large experimental and first-principles (FP) database consisting of (1) bond distances, bond angles, and atomization energies at 0 K of a homologous series of alkanes and their select isomers from methane to n-octane, (2) the potential energy curves of H2, CH, and C2 diatomics, (3) the potential energy curves of hydrogen, methane, ethane, and propane dimers, i.e., (H2)2, (CH4)2, (C2H6)2, and (C3H8)2, respectively, and (4) pressure-volume-temperature (PVT) data of a dense high-pressure methane system with the density of 0.5534 g cc(-1). We compared the atomization energies and geometries of a range of linear alkanes, cycloalkanes, and free radicals calculated from the MEAM potential to those calculated by other commonly used reactive potentials for hydrocarbons, i.e., second-generation reactive empirical bond order (REBO) and reactive force field (ReaxFF). MEAM reproduced the experimental and/or FP data with accuracy comparable to or better than REBO or ReaxFF. The experimental PVT data for a relatively large series of methane, ethane, propane, and butane systems with different densities were predicted reasonably well by the MEAM potential. Although the MEAM formalism has been applied to atomic systems with predominantly metallic bonding in the past, the current work demonstrates the promising extension of the MEAM potential to covalently bonded molecular systems, specifically saturated hydrocarbons and saturated hydrocarbon-based polymers. The MEAM potential has already been parameterized for a large number of metallic unary, binary, ternary, carbide, nitride, and hydride systems, and extending it to saturated hydrocarbons provides a reliable and transferable potential for atomistic/molecular studies of complex material phenomena involving hydrocarbon-metal or polymer-metal interfaces, polymer-metal nanocomposites, fracture and failure in hydrocarbon-based polymers, etc. The latter is especially true since MEAM is a reactive potential that allows for dynamic bond formation and bond breaking during simulation. Our results show that MEAM predicts the energetics of two major chemical reactions for saturated hydrocarbons, i.e., breaking a C-C and a C-H bond, reasonably well. However, the current parameterization does not accurately reproduce the energetics and structures of unsaturated hydrocarbons and, therefore, should not be applied to such systems.

Novel Nucleophiles Enhance the Human Serum Paraoxonase 1 (PON1)-mediated Detoxication of Organophosphates

Paraoxonase 1 (PON1) is a calcium-dependent hydrolase associated with serum high-density lipoprotein particles. PON1 hydrolyzes some organophosphates (OPs), including some nerve agents, through nucleophilic attack of hydroxide ion (from water) in the active site. Most OPs are hydrolyzed inefficiently. This project seeks to identify nucleophiles that can enhance PON1-mediated OP degradation. A series of novel nucleophiles, substituted phenoxyalkyl pyridinium oximes, has been synthesized which enhance the degradation of surrogates of sarin (nitrophenyl isopropyl methylphosphonate; NIMP) and VX (nitrophenyl ethyl methylphosphonate; NEMP). Two types of in vitro assays have been conducted, a direct assay using millimolar concentrations of substrate with direct spectrophotometric quantitation of a hydrolysis product (4-nitrophenol) and an indirect assay using submicromolar concentrations of substrate with quantitation by the level of inhibition of an exogenous source of acetylcholinesterase from non-hydrolyzed substrate. Neither NIMP nor NEMP is hydrolyzed effectively by PON1 if one of these novel oximes is absent. However, in the presence of eight novel oximes, PON1-mediated degradation of both surrogates occurs. Computational modeling has created a model of PON1 embedded in phospholipid and has indicated general agreement of the binding enthalpies with the relative efficacy as PON1 enhancers. PON1 enhancement of degradation of OPs could be a unique and unprecedented mechanism of antidotal action.

Calculations of relative intensities of fragment ions in the MSMS spectra of a doubly charged penta-peptide

BackgroundCurrently, the tandem mass spectrometry (MSMS) of peptides is a dominant technique used to identify peptides and consequently proteins. The peptide fragmentation inside the mass analyzer typically offers a spectrum containing several different groups of ions. The mass to charge (m/z) values of these ions can be exactly calculated following simple rules based on the possible peptide fragmentation reactions. But the (relative) intensities of the particular ions cannot be simply predicted from the amino-acid sequence of the peptide. This study presents initial work towards developing a theoretical fundamental approach to ion intensity elucidation by utilizing quantum mechanical computations.MethodsMSMS spectra of the doubly charged GAVLK peptide were collected on electrospray ion trap mass spectrometers using low energy modes of fragmentation. Density functional theory (DFT) calculations were performed on the population of ion precursors to determine the fragment ion intensities corresponding to a Boltzmann distribution of the protonation of nitrogens in the peptide backbone amide bonds.ResultsWe were able to a) predict the y and b ions intensities order in concert with the experimental observation; b) predict relative intensities of y ions with errors not exceeding the experimental variation.ConclusionsThese results suggest that the GAVLK peptide fragmentation process in the ion trap mass spectrometer is predominantly driven by the thermodynamic stability of the precursor ions formed upon ionization of the sample. The computational approach presented in this manuscript successfully calculated ion intensities in the mass spectra of this doubly charged tryptic peptide, based solely on its amino acid sequence. As such, this work indicates a potential of incorporating quantum mechanical calculations into mass spectrometry based algorithms for molecular identification.

Nanomechanics of phospholipid bilayer failure under strip biaxial stretching using molecular dynamics

The current study presents a nanoscale in silico investigation of strain rate dependency of membrane (phospholipid bilayer) failure when placed under strip biaxial tension with two planar areas. The nanoscale simulations were conducted in the context of a multiscale modelling framework in which the macroscale damage (pore volume fraction) progression is delineated into pore nucleation (number density of pores), pore growth (size of pores), and pore coalescence (inverse of nearest neighbor distance) mechanisms. As such, the number density, area fraction, and nearest neighbor distances were quantified in association with the stress–strain behavior. Deformations of a 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC) bilayer were performed using molecular dynamics to simulate mechanoporation of a neuronal cell membrane due to injury, which in turn can result in long-term detrimental effects that could ultimately lead to cell death. Structures with 72 and 144 phospholipids were subjected to strip biaxial tensile deformations at multiple strain rates. Formation of a water bridge through the phospholipid bilayer was the metric to indicate structural failure. Both the larger and smaller bilayers had similar behavior regarding pore nucleation and the strain rate effect on pore growth post water penetration. The applied strain rates, planar area, and cross-sectional area had no effect on the von Mises strains at which pores greater than 0.1 nm2 were detected (0.509 ± 7.8%) or the von Mises strain at failure (e failure = 0.68 ± 4.8%). Additionally, changes in bilayer planar and cross-sectional areas did not affect the stress response. However, as the strain rate increased from 2.0 × 108 s−1 to 1.0 × 109 s−1, the yield stress increased from 26.5 MPa to 66.7 MPa and the yield strain increased from 0.056 to 0.226.

Interatomic Potential for Hydrocarbons on the Basis of the Modified Embedded-Atom Method with Bond Order (MEAM-BO)

In this paper, we develop a new modified embedded atom method (MEAM) potential that includes the bond order (MEAM-BO) to describe the energetics of unsaturated hydrocarbons (double and triple carbon bonds) and also develop improved parameters for saturated hydrocarbons from those of our previous work. Such quantities like bond lengths, bond angles, and atomization energies at 0 K, dimer molecule interactions, rotational barriers, and the pressure-volume-temperature relationships of dense systems of small molecules give a comparable or more accurate property relative to experimental and first-principles data than the classical reactive force fields REBO and ReaxFF. Our extension of the MEAM potential for unsaturated hydrocarbons (MEAM-BO) is a step toward developing more reliable and accurate polymer simulations with their associated structure-property relationships, such as reactive multicomponent (organic/metal) systems, polymer-metal interfaces, and nanocomposites. When the constants for the BO are zero, MEAM-BO reduces to the original MEAM potential. As such, this MEAM-BO potential describing the interaction of organic materials with metals within the same MEAM formalism is a significant advancement for computational materials science.

Effect of graphene dispersion on the equilibrium structure and deformation of graphene/eicosane composites as surrogates for graphene/polyethylene composites: a molecular dynamics simulation

Molecular dynamics simulations are used to investigate the effect of graphene dispersion on the equilibrium structure and deformation of graphene/eicosane composites. Two graphene sheets with four different interlayer distances are incorporated, respectively, into a eicosane matrix to form graphene/eicosane composites representing different graphene dispersions. With greater graphene dispersion, the “adsorption solidification” of the eicosane increases, where eicosane molecular lamination, orientation, and extension become more uniform and stronger. In addition, eicosane molecular motion is inhibited more in the direction perpendicular to graphene surfaces. When these graphene/eicosane composites are deformed, the free volume initially increases slowly due to small, scattered voids. After reaching the yield strains, the free volume rises sharply as the structures of composites are damaged, and small voids merge into large voids. The damage always occurs in the region of the composite with the weakest “adsorption solidification.” Since this effect is stronger when the graphene sheets are more dispersed, more complete dispersion results in higher composite yield stresses. Lessons from these simulations may provide some insights into graphene/polyethylene composites, where suitable models would require very long equilibration times.

Molecular dynamics simulations of the aggregation behaviour of overlapped graphene sheets in linear aliphatic hydrocarbons

Abstract Molecular dynamics simulations were used to investigate the aggregation of two partially overlapped graphene sheets in hexane, dodecane and eicosane. When partially overlapped graphene sheets are adjacent to one another, they will expel the adsorbed layers of the solvent molecules on the graphene surface, and the amount of overlap will increase. When the overlapped regions of the graphene sheets are separated by solvent molecules, they cannot expel the adsorption layers between them, and so the sheets remain separated. The driving force for aggregation is the van der Waals interaction between the two graphene sheets, while the van der Waals interaction between the graphene sheets and the solvent molecules inhibits graphene aggregation. The diffusion rate of the hydrocarbon molecules with shorter chain lengths is higher. Thus, they diffuse faster during graphene aggregation, which leads to a higher rate of graphene overlapping in the shorter hydrocarbons. This work provides useful insights into graphene aggregation in linear hydrocarbon solvents of varying lengths at the nanoscale.