Nonbonded Contributions Research Articles

Effects of biopolymer ratio and pH value on the complex formation between whey protein isolates and soluble Auricularia auricular polysaccharides

Biopolymer complexes fabricated by proteins and neutral polysaccharides have some specific and innovative functionalities. A better understanding of the interactions among these biopolymers might provide new insight into the applications of the complexes. Therefore, this study aimed to investigate the structural characteristics and molecular interaction mechanisms of whey protein isolates (WPI) and <i>Auricularia auricular</i> polysaccharides (APs). The turbidity analysis confirmed that the pH value and mixing ratio of the two polymers had strong effects on the formation of the APs-WPI complexes. All dispersions formed soluble complexes at approximately pH = 6.0 (pH_c). APs-WPI self-assembles exhibited physically cross-linked networks under higher APs proportions, while they formed spherical complexes at higher WPI ratios. The addition of APs could alter the secondary structure of WPI, and the most noticeable changes were located in the regions of <i>β</i>-sheet and <i>β</i>-turn as confirmed by circular dichroism (CD) analysis. A molecular docking study showed that the amino acid residues of <i>β</i>-lactoglobulin complexed with the –COOH and –OH groups of APs. Hydrogen bonds and hydrophobic interactions, which were nonbonding contributions, played a key role in the formation of the APs-WPI complex. This study provided a basis for the development and application of APs in WPI-based beverages.

Comparison of all atom and united atom models for thermal transport calculations of amorphous polyethylene

Polymer simulations routinely employ models with different molecular resolutions. United atom (UA) models are one such example, where groups of certain atoms in a molecule are clustered into superatoms. Although their computational simplicity makes them particularly attractive for studying a wide range of polymer properties, the missing degrees of freedom in UA models can impact certain properties that are intimately linked to localized vibrations, such as the heat capacity and the thermal transport coefficient κ. In contrast, the numerically exhausting all atom (AA) models produce results that better match experimental data. In this work, we systematically investigate and compare κ obtained from an AA and a UA models for an amorphous polyethylene system. The results indicate that the UA description may not be a suitable model for evaluating thermal transport, since it underestimates κ in comparison to an AA description and the experimental value. The coarse-graining leads to the softer interactions and its presence is highlighted in a weaker mechanical response from the UA model, thus also underestimates κ. We further consolidate our findings by extracting the bonded and the nonbonded contributions to κ within the framework of the single chain energy transfer model.

Exploring the substructural space of indole-3-carboxamide derivatives binding to renin: a novel active-site spatial partitioning approach

Renin has recently attracted much attention in the antihypertensive community, since this enzyme starts the angiotensin-converting cascade and forms the rate-limiting step in this cascade. In the present study, we describe a new method called active-site spatial partitioning (ASSP) for quantitatively characterizing the nonbonding interaction profile between renin and the substructures of indole-3-carboxamide derivatives-a novel class of achiral renin inhibitors that exhibit both high affinity and strong specificity for renin, thus blocking its active state-on the basis of structural models of protein-ligand complexes. It is shown that the ASSP-derived potential parameters are highly correlated with the experimentally measured activities of indole-3-carboxamides; the statistical models linking the parameters and activities using a sophisticated partial least squares regression technique show much promise as an effective and powerful tool for generalizing and predicting the pharmaceutical potencies and the physicochemical properties of other modified derivatives. Furthermore, by visually examining substructure-color plots generated by the ASSP procedure, it is found that the relative importance of nonbonding contributions to the recognition and binding of a ligand by renin is as follows: steric < hydrophobic < electrostatic. The polar and charged moieties that float on the surface of the ligand molecule play a critical role in conferring electrostatic stability and specificity to renin-ligand complexes, whereas the aromatic rings embedded in the core region of the ligand are the main source of hydrophobic and steric potentials that lead to substantial stabilization of the complex architecture.

Evolution of Amide Stacking in Larger γ-Peptides: Triamide H-Bonded Cycles

The single-conformation spectroscopy of two model γ-peptides has been studied under jet-cooled conditions in the gas phase. The methyl-capped triamides, Ac-γ(2)-hPhe-γ(2)-hAla-NHMe and Ac-γ(2)-hAla-γ(2)-hPhe-NHMe, were probed by resonant two-photon ionization (R2PI) and resonant ion-dip infrared (RIDIR) spectroscopies. Four conformers of Ac-γ(2)-hPhe-γ(2)-hAla-NHMe and three of Ac-γ(2)-hAla-γ(2)-hPhe-NHMe were observed and spectroscopically interrogated. On the basis of comparison with the predictions of density functional theory calculations employing a dispersion-corrected functional (ωB97X-D/6-311++G(d,p)), all seven conformers have been assigned to particular conformational families. The preference for formation of nine-membered rings (C9) observed in a previous study [James, W. H., III et al., J. Am. Chem. Soc. 2009, 131, 14243] of the smaller analog, Ac-γ(2)-hPhe-NHMe, carries over to these triamides, with four of the seven conformers forming C9/C9 sequential double-ring structures, and one conformer a C9/C14 bifurcated double ring. The remaining two conformers form C7/C7/C14 H-bonded cycles involving all three amide NH groups, unprecedented in other peptides and peptidomimetics. The amide groups in these structures form a H-bonded triangle with the two trimethylene bridges forming loops above and below the molecule's midsection. The structure is a natural extension of amide stacking, with the two terminal amides blocked from forming the amide tristack by formation of the C14 H-bond. Pair interaction energy decomposition analysis based on the fragment molecular orbital method (FMO-PIEDA) is used to determine the nonbonded contributions to the stabilization of these conformers. Natural bond orbital (NBO) analysis identifies amide stacking with a pair of n → π* interactions between the nitrogen lone pairs and π* orbitals on the carbonyl of the opposing amide groups.

Calculation of single chain cellulose elasticity using fully atomistic modeling

Cellulose nanocrystals, a potential base material for green nanocomposites, are ordered bundles of cellulose chains. The properties of these chains have been studied for many years using atomic-scale modeling. However, model predictions are difficult to interpret because of the significant dependence of predicted properties on model details. The goal of this study is to begin to understand these dependencies. We focus on the investigation on model cellulose chains with different lengths and having both periodic and nonperiodic boundary conditions, and predict elasticity in the axial (chain) direction with three commonly used calculation methods. We find that chain length, boundary conditions, and calculation method affect the magnitude of the predicted axial modulus and the uncertainty associated with that value. Further, the axial modulus is affected by the degree to which the molecule is strained. This result is interpreted in terms of the bonded and nonbonded contributions to potential energy, with a focus on the breaking of hydrogen bonds during deformation.

Side-chain conformational space analysis (SCSA): A multi conformation-based QSAR approach for modeling and prediction of protein–peptide binding affinities

In this article, the concept of multi conformation-based quantitative structure-activity relationship (MCB-QSAR) is proposed, and based upon that, we describe a new approach called the side-chain conformational space analysis (SCSA) to model and predict protein-peptide binding affinities. In SCSA, multi-conformations (rather than traditional single-conformation) have received much attention, and the statistical average information on multi-conformations of side chains is determined using self-consistent mean field theory based upon side chain rotamer library. Thereby, enthalpy contributions (including electrostatic, steric, hydrophobic interaction and hydrogen bond) and conformational entropy effects to the binding are investigated in terms of occurrence probability of residue rotamers. Then, SCSA was applied into the dataset of 419 HLA-A 0201 binding peptides, and nonbonding contributions of each position in peptide ligands are well determined. For the peptides, the hydrogen bond and electrostatic interactions of the two ends are essential to the binding specificity, van der Waals and hydrophobic interactions of all the positions ensure strong binding affinity, and the loss of conformational entropy at anchor positions partially counteracts other favorable nonbonding effects.

Computational investigation of pressure profiles in lipid bilayers with embedded proteins

The distribution of surface tension within a lipid bilayer, also referred to as the lateral pressure profile, has been the subject of theoretical scrutiny recently due to its potential to radically alter the function of biomedically important membrane proteins. Experimental measurements of the pressure profile are still hard to come by, leaving first-principles all-atom calculations of the profile as an important investigative tool. We describe and validate an efficient implementation of pressure profile calculations in the molecular dynamics package NAMD, capable of distinguishing between internal, bonded and nonbonded contributions as well as those of selected atom groups. The new implementation can also be used in conjunction with Ewald summation for long-range electrostatics, improving the accuracy and reproducibility of the calculated profiles. We then describe results of the calculation of a pressure profile for a simple protein–lipid system consisting of melittin embedded in a DMPC bilayer. While the lateral pressure in the protein–lipid system is nearly the same as that of the bilayer alone, partitioning of the lateral pressure by atom type revealed substantial perturbation of the pressure profile and surface tension in an asymmetric manner.

Kinetic Energy and the Covalent Bond in H2+

A modified version of Ruedenberg’s innovative analysis of the chemical bond in the hydrogen molecule ion is presented that factors the bond energy into bonding and nonbonding contributions. This simplified approach clearly illustrates Ruedenberg’s main thesis: chemical bond formation is driven by a decrease in electron kinetic energy.

Computational Protein Design Is a Challenge for Implicit Solvation Models

Increasingly complex schemes for representing solvent effects in an implicit fashion are being used in computational analyses of biological macromolecules. These schemes speed up the calculations by orders of magnitude and are assumed to compromise little on essential features of the solvation phenomenon. In this work we examine this assumption. Five implicit solvation models, a surface area-based empirical model, two models that approximate the generalized Born treatment and a finite difference Poisson-Boltzmann method are challenged in situations differing from those where these models were calibrated. These situations are encountered in automatic protein design procedures, whose job is to select sequences, which stabilize a given protein 3D structure, from a large number of alternatives. To this end we evaluate the energetic cost of burying amino acids in thousands of environments with different solvent exposures belonging, respectively, to decoys built with random sequences and to native protein crystal structures. In addition we perform actual sequence design calculations. Except for the crudest surface area-based procedure, all the tested models tend to favor the burial of polar amino acids in the protein interior over nonpolar ones, a behavior that leads to poor performance in protein design calculations. We show, on the other hand, that three of the examined models are nonetheless capable of discriminating between the native fold and many nonnative alternatives, a test commonly used to validate force fields. It is concluded that protein design is a particularly challenging test for implicit solvation models because it requires accurate estimates of the solvation contribution of individual residues. This contrasts with native recognition, which depends less on solvation and more on other nonbonded contributions.

Identification of pyrite valence band contributions using synchrotron-excited X-ray photoelectron spectroscopy

The major contributions to the pyrite valence band have been identified experimentally by monitoring XPS valence band signal intensity as a function of photon (X-ray source) energy. The S-S σ and σ* orbitals are located at about 13 and 16 eV binding energy and are almost exclusively derived from S 3s-S 3s mixing; there is no experimental evidence for a S 3p contribution to these molecular orbital (molecular orbital) values as required for sp3 hybridization. Fe-S σ (Fe 3deg-S 3pz derived) and Fe-S π and π* (Fe 3dt2g-S 3px,y derived) molecular orbitals are identified at Binding Energies (B.E.) less than 8 eV, and are consistent with energies calculated by Eyert et al. (1998). Fe-S π molecular orbital contributions are located in the valence band between about 1.8 and 3 eV and Fe-S π* molecular orbitals contribute between about 0.7 to 1.5 eV binding energy. Contributions observed at the top of the valence band and concentrated between the Fermi level and about 0.6 eV B.E. may be derived from Fe 3deg (non-bonding) orbitals. The experimental data are consistent with these non-bonding contributions being derived from surface Fe species (Fe electronic surface states), and perhaps represent the Fe 3deg “dangling bonds” produced by rupture of Fe-S σ bonds during fracture. The conformity of spectral assignments based on experimental data with band theoretical calculations (of Eyert et al. 1998, using a basis set appropriate to pyrite) indicates that the essential aspects of the pyrite valence band are understood and energetically quantified. Additional study is required to identify positively.

Deformation of Elastomeric Networks: Relation between Molecular Level Deformation and Classical Statistical Mechanics Models of Rubber Elasticity

In this work a specialized molecular simulation code has been used to provide details of the underlying micromechanisms governing the observed macroscopic behavior of elastomeric materials. In the simulations the polymer microstructure was modeled as a collection of unified atoms interacting by two-body potentials of bonded and non-bonded type. Representative Volume Elements (RVEs) containing a network of 200 molecular chains of 100 bond lengths are constructed. The evolution of the RVEs with uniaxial deformation was studied with molecular dynamics techniques. The simulations enable observation of structural features with deformation including bond lengths and angles as well as chain lengths and angles. The simulations also enable calculation of the macroscopic stress-strain behavior and its decomposition into bonded and non-bonded contributions. The distribution in initial end-to-end chain lengths is consistent with Gaussian statistics treatments of rubber elasticity. It is shown that application of an axial strain of +/ 0.7 (a logarithmic strain measure is used) only causes a change in the average bond angle of /+ 5 degrees indicating the freedom of bonds to sample space at these low-moderate deformations; the same strain causes the average chain angle to change by /+ 20 degrees. Randomly selected individual chains are monitored during deformation; their individual chain lengths and angles are found to evolve in an essentially ane manner consistent with Gaussian statistics treatments of rubber elasticity. The average chain length and angle are found to evolve in a manner consistent with the eight-chain network model of elasticity. Energy quantities are found to remain constant during deformation consistent with the nature of rubber elasticity begin entropic in origin. The stress-strain response is found to have important bonded and non-bonded contributions. The bonded contributions arise from the rotations of the bonds toward the maximum principal stretch axis(es) in tensile(compressive) loading.

Analysis of Coupling Schemes in Free Energy Simulations: A Unified Description of Nonbonded Contributions to Solvation Free Energies

The solvation free energies evaluated from molecular simulations with explicit solvent models and integral equation methods are compared to the results obtained from macroscopic models. Different p...

Analytical potential energy surface for methane in terms of interatomic forces

Ab initio bending potentials for methane are compared to potentials for the mutual interaction of non-bonded hydrogen atoms. Bonding and non-bonding contributions have been incorporated in a simple, analytical expression for the dependence of potential energy on molecular geometry. The expression, with four fixed and ten fitted parameters, agrees with 112 ab initio points within a root-mean-square deviation of 4 kJ mol −1. Variational transition-state theory rate constants and harmonic vibrational frequencies have been calculated from the fitted potential surface. For the functional form used, non-bonded repulsions between hydrogen atoms contribute 29% to the bending force constant at the potential minimum, reduce the bond dissociation energy by 120 kJ mol −1 and cause the formation of a potential energy ridge when H approaches the edge of CH 3.

Charge distributions and chemical effects. XXII. On the partitioning of molecular energies and the relationships between energy components

The exact quantum mechanical formulation of atomic and molecular energies and the postulate that ’’chemical bonds’’ exist combine to show that the nuclear–electronic and nuclear–nuclear potential energy V (k,mol) involving the kth atom in a molecule is for its largest part determined by ’’local effects’’ related to the number and type of bonds formed by k. These local effects are measured by the derivatives ∂εkj/∂Zk of the bond energies εkj involving k, with respect to its nuclear charge Zk. To a good approximation, neglecting the small nonbonded contributions, V (k,mol) =Vne (free atom k)−Zkj𝒥∂εkj/∂Zk. Applications to saturated hydrocarbons at the level of experimental accuracy indicate that the Emol/(Vne+2Vnn) ratios derived in this manner are close to their ab initio counterparts. These ratios are averages KmolAv=𝒥KmolkV (k,mol)/𝒥V (k,mol) of the ratios Kmolk=Ek(mol)/V (k,mol) defining the individual total energies Ek(mol) of atoms being part of a molecule, whereby Emol=𝒥Ek(mol). The Kmolk’s, in turn, are shown to be constants in saturated hydrocarbons, i.e., 1/2.3329 for C and 1/2 for H, and are instrumental in accurate calculations of molecular energies, Emol=𝒥Kmolk V (k,mol), and for deriving energy differences, Ek(free atom)−Ek(mol) =ΔEk =kmolkZk𝒥∂εkj/∂Zk +(Katomk−Kmolk) Vne(free atom k), between free and bonded atoms. Positive ΔEk values indicate that both the carbon and the hydrogen atoms are more stable in their bonded states than the free atoms, which is now understood in terms of dominating local binding properties, rather than in terms of local electron populations which play only a minor, though chemically significant, part on the scale of molecular energies.

On the contributions of resonance, hybridization and nonbonded interactions to the structure of butadiene

A recent ab initio molecular orbital calculation on butadiene has been interpreted by Skaarup, Boggs and Skancke as indicating that the shortness of the central C-C bond is due primarily to hybridization. Resonance was considered to make a minor contribution and nonbonded interactions were judged to be unimportant. Unfortunately, this analysis failed to take into account the crucial role of geminal nonbonded interactions, and the calculations were, accordingly, not designed to discriminate between the hybridization and nonbonded models. A more direct investigation of intramolecular nonbonded interactions based on ab initio computations has been earned out on other systems, however, providing evidence that the effects of nonbonded contributions are substantial.