vdW Energies Research Articles

The adsorption of p-hydroxybenzoic acid on graphene oxide under different pH and in-situ desorption in direct current electric field

The development and ongoing optimization of measures to reduce and eliminate p-hydroxybenzoic acid (p-HBA) in industrial wastewater are significant due to its potential carcinogenic effect and bio-recalcitrant. Graphene oxide (GO) is an ideal adsorbent for removing aromatic acids and achieving adsorbent recovery and resource conservation. In this study, the adsorption properties of p-HBA onto GO at different pH values and the regeneration mechanism of adsorbent under varying electric field intensities were analyzed using molecular dynamics (MD) simulation. The simulation results demonstrate that GO exhibits preferable adsorption capabilities for p-HBA at low pH, and van der Waals (vdW) interaction plays a leading role. However, the adsorption stability decreases at high pH (particularly pH > 9.3) with most p-HBA desorption from the GO surface. When an electric field of 1.0 V/nm is applied to the acidic system (HGO_HBA_HBA−), the total adsorption interaction energy between GO and p-HBA decreases but remains high (−1836.93 kJ/mol). When a 0.6 V/nm electric field is added to the alkaline system (GO2−_HBA2−), the vdW and electrostatic interaction energies are recorded as −35.34 kJ/mol and 3546.97 kJ/mol. The vdW interaction is weak, and electrostatic repulsion increases, facilitating the desorption of p-HBA from the GO surface. This work aims to share insights into the microscopic removal mechanism of p-HBA on the GO surface under different pH values and provide a theoretical perspective on the regeneration mechanism of GO.

Concentration-dependent mechanism of the binding behavior of ibuprofen to the cell membrane: A molecular dynamic simulation study

Ibuprofen is a commonly used drug for treating headaches, pain, and fever. The lipid bilayer is the primary and most important interface for drugs to interact with biological systems. However, the molecular interactions between ibuprofen and the cell membrane are not well understood. Our findings suggest that the interactions between ibuprofen and the bilayer involve multiple steps and depend on the concentration of the drug. At low concentrations of ibuprofen, it can bind to the surface of the lipid bilayer. The electrostatic and vdW energies of IBU-lipid at 0 ns of the simulation were −22.5 ± 3.2 and −5.9 ± 1.2 kj.mol-1 Fig. 2. In the following, the vdW energy of the IBU-lipid was increased by around −134.6 ± 3.7 kj.mol-1 whereas the electrostatic energy of the IBU-lipid was significantly decreased. This binding is facilitated by electrostatic and vdW interactions between ibuprofen and the head group of lipids. In the second step, ibuprofen is inserted into the lipid bilayer and positioned at the interface between the bilayer and the aqueous phase. In high concentrations of ibuprofen, it moved to the central region of the lipid bilayer. At this concentration, the physical and structural properties of the cell membrane change significantly. Results from the radial distribution function analysis indicate that at low concentrations, ibuprofen molecules are situated close to the head groups of phosphate groups. However, at high concentrations of ibuprofen, these molecules move to the inner side of the lipid bilayer. In addition, our findings indicate that at low concentrations of ibuprofen, these molecules did not significantly alter the physical properties of the cell membrane. In contrast, at high concentrations of ibuprofen, the physical parameters of the hydrocarbon tails, such as thickness, fluidity, and order, changed dramatically. APL parameter for POPC membrane increased slightly to 0.60 and 0.63 nm2 in the presence of low and high concentrations of ibuprofen molecules. The three-step interaction between ibuprofen and the lipid bilayer involves several events, such as the movement of ibuprofen molecules towards the central region of the lipid bilayer and the deformation and alteration of the structural and stability properties of the cell membrane. These effects are observed only at high concentrations of ibuprofen. It appears that the side effects of ibuprofen overdose are related to changes in the properties of the cell membrane and, subsequently, the function of membrane-anchored target proteins.

The van der Waals interaction and absorption and electron circular dichroism spectra of two-dimensional bilayer stacked structures

van der Waals (vdW) heterojunctions based on two-dimensional (2D) materials, graphene and transition metal dichalcogenides (TMDs), are a research hotspot for future optoelectronic and exciton devices. Bond-free vdW interactions are key to 2D material heterojunction device reliability and stability. However, most of the current research on 2D stacked materials heterostructures mainly focuses on optical properties and electronic structure. Furthermore, vdW interaction in 2D heterostructures is studied and understood on the basis of qualitative description and energy ranges from the literature. There are few studies on the nature of vdW interaction based on practical calculations of the quantitative strength and microscopic mechanism of vdW interaction between 2D stacked materials. Therefore, this paper explores the vdW interaction between 2D material stacked bilayer structures, including bilayer graphene, graphene/MoS2 and graphene/WS2 heterostructures, focusing on quantitative analysis of the energy components of the vdW interaction. We first visually observed the weak interactions in the three stacked bilayer structures through noncovalent interaction (NCI) analysis, and found that the interactions are concentrated in the binding region between the two-layer structures. We mainly decomposed the weak interaction energy in the three 2D material bilayer heterostructures through energy decomposition analysis based on the force field (EDA-FF) method and obtained the energy values and proportions of the three components-electrostatic energy, exchange repulsion energy and dispersion energy of the total binding energy between the 2D stacked bilayer structures. The vdW interaction energy is the sum of the exchange repulsion energy and dispersion energy, and the dispersion energy of the vdW interaction accounts for more than 60% of the binding energy of the weak interaction between the 2D bilayer stacked structures. The vdW strengths in the bilayer structures are on the order of 177.07, 123.85, and 133.93 kJ/mol, approxmately 1–2 orders of magnitude larger than the classically defined vdW energies of 0.1–10 kJ/mol. Furthermore, we calculate the density of states of the three 2D stacked structures, and further obtained HOMO-LOMO information; to further understand the electronic structures of the graphene/MoS2 and graphene/WS2 heterostructures, we calculated their optical absorption spectra and electron circular dichroism (ECD) spectra. According to the calculation results, the two heterostructures have strong absorption peaks in the visible region, and the charge transfer forms at the strong absorption peak can be determined according to the charge transfer diagram. The ECD spectra indicate that the configurations of the graphene/MoS2 and graphene/WS2 heterostructures have large chirality. Our work contributes to a deeper understanding of the nature of the weak interactions and optical properties in 2D stacked materials, which plays a fundamental role in promoting the construction of stable 2D heterostructure configurations and the development of multifunctional 2D devices. The research is conducive to further promoting the basic research and practical development of strong optoelectronic and excitonic 2D heterojunctions devices.

Mild adsorption of carbon nitride (C3N3) nanosheet on a cellular membrane reveals its suitable biocompatibility

Recently, the novel hole-containing carbon nitride C3N3 nanomaterial was successfully synthesized, featuring outstanding and unique mechanical and electrical properties. However, to fully exploit this nanomaterial in biomedical applications, information regarding its biocompatibility is necessary. Herein, by using all-atom molecular dynamics simulations, we evaluate the interactions between a C3N3 nanosheet and a critical cellular component, that is, a lipid membrane bilayer. Our results indicate that the C3N3 nanosheet is able to interact with the lipid bilayer surface without affecting the membrane’s structural integrity. Moreover, our results showed that the C3N3 nanosheet is adsorbed on the surface of the lipid bilayer without inflicting any structural damage to the membrane, regardless of the conditions of the system (that is, with and without restrains in the C3N3 nanosheet). Also, we found that both energy contributions, namely vdW and Coulomb energies, conjointly mediated the C3N3 adsorption process. In comparison and as expected, pristine graphene significantly disturbed the membrane structure. Perpendicularly-oriented-sheet simulations described the significance of the surface charges of the C3N3 nanosheet in prohibiting its insertion into the membrane. Detailed analysis indicated that the electrostatic attraction between the pores in the C3N3 structure and the lipid head amino groups stabilized the interaction restricting the insertion of the C3N3 structure deeper into the membrane. Our results suggested the importance of the negatively charged C3N3 pores when interacting with lipid membranes. Our findings shed light on the potential compatibility of C3N3 with biomembranes and its underlying molecular mechanism, which might provide a useful foundation for the future exploration of this 2D nanomaterial in biomedical applications.

Molecular Dynamics Simulation Studies of the CL-20/DNB Co-crystal Based PBX with HTPB

Molecular dynamics (MD) simulations were conducted for a CL-20/DNB (2, 4, 6, 8, 10, 12-hexanitro-2, 4, 6, 8, 10, 12-hexaazaisowurtzitane/1, 3-dinitrobenzene) co-crystal based PBX (Polymer-bonded explosive) with HTPB (hydroxyl-terminated polybutadiene). The binding energies, pair correlation functions and mechanical properties of the PBX were reported. From the calculated binding energy (E bind), it was found that the order of the binding energies between the crystalline surfaces (1 0 0), (0 1 0) and (0 0 1) and HTPB is (1 0 0) > (0 0 1) > (0 1 0). And it was also shown that the interactions between the crystalline surfaces and HTPB originate mainly from vdW energies. The pair correlation function revealed that H···O hydrogen bonds exist on the interfaces between the crystalline surfaces and HTPB. From the calculated mechanical data, the co-crystal/HTPB was inferred that the PBX has a higher buffer for external stimuli and reduces the formation probability of hot spots.

London Dispersion Corrections to Density Functional Theory for Transition Metals Based on Fitting to Experimental Temperature-Programmed Desorption of Benzene Monolayers.

Standard implementations of generalized gradient approximation (GGA)-based density functional theory (DFT) describe well strongly bound molecules and solids but fail to describe long-range London dispersion or van der Waals (vdW) attraction interactions that are important in molecular crystals and two-dimensional solids. To provide accurate values for the vdW distance and energies for the metals Cu, Ag, Au, Ni, Pd, and Pt, we determined empirical vdW corrections to Perdew, Burke, and Ernzerhof (PBE) DFT by fitting the experimental adsorption enthalpies measured by temperature-programmed desorption (TPD) from benzene monolayers by Campbell and co-workers ( J. Phys. Chem. C 2016, 120, 25161-25172). Benzene physisorbed to these metals without chemical reaction; therefore, we consider the bonding to be vdW. We use the low gradient form for the vdW corrections, EvdW-LG = -C6LG/[R6 + RvdwLG6] with just two parameters per atom (C6LG and RvdwLG). This LG form leads to negligible changes in bond distances and angles, so adjusting the parameters should not sacrifice accuracy for the bonding interactions. We demonstrate that the parameters fitted to benzene also describe well the physisorption enthalpies for other hydrocarbons (naphthalene, cyclohexane, methane, ethane, and propane) on Pt. We also report low gradient vdW correction parameters for the noble gases that fit the equilibrium lattice parameter and heat of vaporization of the crystals.

Therapeutic Path to Double Knockout: Investigating the Selective Dual-Inhibitory Mechanisms of Adenosine Receptors A1 and A2 by a Novel Methoxy-Substituted Benzofuran Derivative in the Treatment of Parkinson's Disease.

The dual inhibition of adenosine receptors A1 (A1 AR) and A2 (A2A AR) has been considered as an efficient strategy in the treatment of Parkinson's disease (PD). This led to the recent development of a series of methoxy-substituted benzofuran derivatives among which compound 3j exhibited dual-inhibitory potencies in the micromolar range. Therefore, in this study, we seek to resolve the mechanisms by which this novel compound elicits its selective dual targeting against A1 AR and A2A AR. Unique to the binding of 3j in both proteins, from our findings, is the ring-ring interaction elicited by A1Phe275 (→ A2Phe170) with the benzofuran ring of the compound. As observed, this π-stacking interaction contributes notably to the stability of 3j at the active sites of A1 and A2A AR. Besides, conserved active site residues in the proteins such as A1Ala170 (→ A2Ala65), A1Ile173 (→ A2Ile68), A1Val191 (→ A2Val86), A1Leu192 (→ A2Leu87), A1Ala195 (→ A2Ala90), A1Met284 (→ A2Met179), A1Tyr375 (→ A2Tyr369), A1Ile378 (→ A2Ile372), and A1His382 (→ A2His376) were commonly involved with other ring substituents which further complement the dual binding and stability of 3j. This reflects a similar interaction mechanism that involved aromatic (π) interactions. Consequentially, vdW energies contributed immensely to the dual binding of the compound, which culminated in high ΔGbinds that were homogenous in both proteins. Furthermore, 3j commonly disrupted the stable and compact conformation of A1 and A2A AR, coupled with their active sites where Cα deviations were relatively high. Ligand mobility analysis also revealed that both compounds exhibited a similar motion pattern at the active site of the proteins relative to their optimal dual binding. We believe that findings from this study with significantly aid the structure-based design of highly selective dual-inhibitors of A1 and A2A AR.

DLVO Interaction Energies for Hollow Particles: The Filling Matters.

A thorough knowledge of the interaction energy between a hollow particle (HP) and a surface or between two HPs is critical to the optimization of HP-based products and assessing the environmental risks of HPs and HP-associated pollutants. The van der Waals (vdW) energy between a HP and a surface is often calculated by subtracting the vdW energies of the inner and outer HP geometries. In this study, we show that this subtraction method is only valid when the interior and exterior fluids are the same, for example, for water-filled HPs (WHPs) dispersed in an aqueous solution. Expressions were developed to calculate the vdW energies for HPs whose interiors were filled with air (AHPs). The vdW energies were then calculated between a planar surface and a spherical or cylindrical WHP and AHP, and between WHPs or AHPs. The vdW attraction between a surface and a WHP was decreased at large separation distances compared to solid particles, and this reduced the depth of the secondary minimum. In contrast, the vdW attraction for AHPs and a surface was significantly reduced at all separation distances, and even became repulsive for thin shells, and this inhibited both primary and secondary minimum interactions. The vdW attraction between WHPs decreased with increasing shell thicknesses, and this reduced aggregation in both primary and secondary minima. In contrast, aggregation of AHPs was increased in both minima with decreasing shell thicknesses because of an increase in vdW attraction. Our theoretical calculations show the evolution of vdW and total interaction energies for HPs with different interior fluids and shell thicknesses. These results help explain various experimental observations such as inhibited attachment and favorable aggregation for AHPs (e.g., carbon nanotubes) and favorable bubble coalescence.

Protein-protein interfaces are vdW dominant with selective H-bonds and (or) electrostatics towards broad functional specificity.

Several catalysis, cellular regulation, immune function, cell wall assembly, transport, signaling and inhibition occur through Protein- Protein Interactions (PPI). This is possible with the formation of specific yet stable protein-protein interfaces. Therefore, it is of interest to understand its molecular principles using structural data in relation to known function. Several interface features have been documented using known X-ray structures of protein complexes since 1975. This has improved our understanding of the interface using structural features such as interface area, binding energy, hydrophobicity, relative hydrophobicity, salt bridges and hydrogen bonds. The strength of binding between two proteins is dependent on interface size (number of residues at the interface) and thus its corresponding interface area. It is known that large interfaces have high binding energy (sum of (van der Waals) vdW, H-bonds, electrostatics). However, the selective role played by each of these energy components and more especially that of vdW is not explicitly known. Therefore, it is important to document their individual role in known protein-protein structural complexes. It is of interest to relate interface size with vdW, H-bonds and electrostatic interactions at the interfaces of protein structural complexes with known function using statistical and multiple linear regression analysis methods to identify the prominent force. We used the manually curated non-redundant dataset of 278 hetero-dimeric protein structural complexes grouped using known functions by Sowmya et al. (2015) to gain additional insight to this phenomenon using a robust inter-atomic non-covalent interaction analyzing tool PPCheck (Anshul and Sowdhamini, 2015). This dataset consists of obligatory (enzymes, regulator, biological assembly), immune and nonobligatory (enzyme and regulator inhibitors) complexes. Results show that the total binding energy is more for large interfaces. However, this is not true for its individual energy factors. Analysis shows that vdW energies contribute to about 75% ± 11% on average among all complexes and it also increases with interface size (r2 ranging from 0.67 to 0.89 with p<0.01) at 95% confidence limit irrespective of molecular function. Thus, vdW is both dominant and proportional at the interface independent of molecular function. Nevertheless, H bond energy contributes to 15% ± 6.5% on average in these complexes. It also moderately increases with interface size (r2 ranging from 0.43 to 0.61 with p<0.01) only among obligatory and immune complexes. Moreover, there is about 11.3% ± 8.7% contribution by electrostatic energy. It increases with interface size specifically among non-obligatory regulator-inhibitors (r2 = 0.44). It is implied that both H-bonds and electrostatics are neither dominant nor proportional at the interface. Nonetheless, their presence cannot be ignored in binding. Therefore, H-bonds and (or) electrostatic energy having specific role for improved stability in complexes is implied. Thus, vdW is common at the interface stabilized further with selective H-bonds and (or) electrostatic interactions at an atomic level in almost all complexes. Comparison of this observation with residue level analysis of the interface is compelling. The role by H-bonds (14.83% ± 6.5% and r2 = 0.61 with p<0.01) among obligatory and electrostatic energy (8.8% ± 4.77% and r2 = 0.63 with p <0.01) among non-obligatory complexes within interfaces (class A) having more non-polar residues than surface is influencing our inference. However, interfaces (class B) having less non-polar residues than surface show 1.5 fold more electrostatic energy on average. The interpretation of the interface using inter-atomic (vdW, H-bonds, electrostatic) interactions combined with inter-residue predominance (class A and class B) in relation to known function is the key to reveal its molecular principles with new challenges.

All-atom molecular dynamics analysis of multi-peptide systems reproduces peptide solubility in line with experimental observations

In order to investigate the contribution of individual amino acids to protein and peptide solubility, we carried out 100 ns molecular dynamics (MD) simulations of 106 Å3 cubic boxes containing ~3 × 104 water molecules and 27 tetra-peptides regularly positioned at 23 Å from each other and composed of a single amino acid type for all natural amino acids but cysteine and glycine. The calculations were performed using Amber with a standard force field on a special purpose MDGRAPE-3 computer, without introducing any “artificial” hydrophobic interactions. Tetra-peptides composed of I, V, L, M, N, Q, F, W, Y, and H formed large amorphous clusters, and those containing A, P, S, and T formed smaller ones. Tetra-peptides made of D, E, K, and R did not cluster at all. These observations correlated well with experimental solubility tendencies as well as hydrophobicity scales with correlation coefficients of 0.5 to > 0.9. Repulsive Coulomb interactions were dominant in ensuring high solubility, whereas both Coulomb and van der Waals (vdW) energies contributed to the aggregations of low solubility amino acids. Overall, this very first all-atom molecular dynamics simulation of a multi-peptide system appears to reproduce the basic properties of peptide solubility, essentially in line with experimental observations.

Desulfurization of fuel oils: Mutual solubility of ionic liquids and fuel oil

Extractive and oxidative desulfurization of fuel oil using ionic liquids (ILs) as solvents have been intensively studied recently. In such processes, the mutual solubility of ILs and fuel oil is still a major concern. Less mutual solubility is desired to reduce the loss of ILs and the contamination of fuel oil. To screen the ideal ILs with less mutual solubility with fuel oil and to understand the effects of ILs structural characteristics on the mutual solubility, we employed Conductor-like Screening Model for Real Solvents (COSMO-RS) to calculate the mutual solubility of 1830 ILs and model fuel oil. The influences of ILs structural characteristics such as cationic nature, cationic alkyl chain length, cationic symmetry, anionic nature, anionic alkyl chain length and functional group on the mutual solubility are investigated from micro-level view with σ-profile, σ-moment and COSMO-RS energies. The mutual solubility is strongly dependent on cation or anion species and is highly influenced by van der Waals (vdW) and hydrogen-bonding (HB) energies. Cations with smaller non-polarity, shorter alkyl chain length and less symmetry tend to have weaker vdW energies and smaller mutual solubility, while anions with larger polarity tend to have stronger HB energies and smaller mutual solubility. The functional groups also show remarkable effects on mutual solubility; those functional groups that decrease the non-polarity and vdW energies or increase the polarity and HB energies favor the small mutual solubility. Moreover, experimental determinations of the mutual solubility indicate [C1pyr]H2PO4 is a good solvent for desulfurization. This work provides the theoretical basis to design and select the ILs, which have small mutual solubility with fuel oil.

Assessing the reliability of van der Waals DFT functionals to study the physisorption of molecular hydrogen on aromatic systems

The physisorption of $$\hbox {H}_2$$ on organic molecules has received much attention during the 2000s, because they are the elementary bricks of the organic linkers in isoreticular metal–organic frameworks, materials that are considered as very promising ones for hydrogen storage. Here, we have studied the physisorption of $$\hbox {H}_2$$ on a wide variety of aromatic molecules, from pure and substituted benzene to polycyclic hydrocarbons, by means of density functional theory (DFT). In performing DFT calculations, we have taken of the relatively new family of functionals that include van der Waals (vdW) effects. We have performed our calculations with two different approaches: (1) the one proposed by Grimme et al. (J Chem Phys 132:154104, 2011), DFT+D3, which corrects the total energy; (2) the one proposed by Lundqvist et al. (Phys Rev B 82:081101, 2010), vdW+DF2, which corrects the correlation energy. From the comparison between our DFT vdW energies and the ones obtained by means of ab initio theory methods [MP2 and CCSD(T)], we conclude that DFT in combination with the vdW+DF2 functional yields reliable binding energies of $$\hbox {H}_2$$ to aromatic complexes, at a much smaller computational cost. Hopefully, our results will stimulate further studies on these kinds of systems, which have been hampered due to limited computational resources.

Van der Waals Effects on semiconductor clusters.

Van der Waals (vdW) interactions play an important role on semiconductors in nanoscale. Here, we utilized first-principles calculations based on density functional theory to demonstrate the growth mode transition from prolate to multiunit configurations for Gen (n = 10-50) clusters. In agreement with the injected ion drift tube techniques that "clusters with n < 70 can be thought of as loosely bound assemblies of small strongly bound fragments (such as Ge7 and Ge10 )," we found these stable fragments are connected by Ge6 , Ge9 , or Ge10 unit (from bulk diamond), via strong covalent bonds. Our calculated cations usually fragment to Ge7 and Ge10 clusters, in accordance with the experiment results that the spectra Ge7 and Ge10 correspond to the mass abundance spectra. By controlling a germanium cluster with vdW interactions parameters in the program or not, we found that the vdW effects strengthen the covalent bond from different units more strikingly than that in a single unit. With more bonds between units than the threadlike structures, the multiunit structures have larger vdW energies, explaining why the isolated nanowires are harder to produce. © 2015 Wiley Periodicals, Inc.

Molecular dynamics study of carbon-nanotube shuttle-memory on graphene nanoribbon array

Carbon nanomaterials, such as fullerenes, graphenes, and nanotubes, have a unique place in nanoscience, owing to their exceptional electrical, thermal, chemical and mechanical properties, and the number of their potential applications continues to grow. Conjugated carbon nanomaterials, such as fullerene–nanotube, fullerene–graphene, and nanotube–graphene hybrids, also have great potential applications. In this work, we present the schematics and the energetics of a nonvolatile memory based on nanotube–graphene hybrid, serving as the key building blocks for molecular-scale computers, and investigated the dynamic operations of a double-walled carbon nanotube (CNT) memory element, by using classical molecular dynamics simulations. The localized potential energy wells, achieved from the vdW energies between the outer CNT and two graphene-nanoribbons (GNRs), cause bi-stability of the outer CNT positions; and the alternative driving forces lead to the reversibility of this shuttle memory. Since the attractive vdW potential energies between the outer CNT and GNR make the outer CNT keep its position, the proposed shuttle-memory device can retain its stored data, without recharging processes.

A polyethylene chain investigated with replica exchange molecular dynamics simulation: Equilibrium lamellar thickness and melting point, ordering and free energy

In the present work, a polyethylene chain with N=200 CH2 units was simulated using replica exchange molecular dynamics (REMD). Simulations were performed in a broad temperature range and for intra-chain interactions varying from the fully interacting to the ideal spring chain.Our work demonstrates that REMD is a very efficient method to obtain equilibrium data. It is found that the coil-to-globule transition is dominated by the vdW energy, whereas the globule-to-folded chain transition is accompanied by transitional behavior in the torsion and vdW energies. Our data clearly show that for the chain length considered here, the chain folded crystal to globule transition is a continuous transition. Nevertheless, we can establish with good accuracy the equilibrium transition temperature for the chain folded crystal to globule transition.A set of orientational order parameters was used to investigate the order in the polymer chain. At the globule-to-folded chain transition an abrupt change in the value of the order parameter is observed, whereas there is no or almost no change in the value of the order parameter at the coil-to-globule transition temperature. The (apparent) order in the disordered globular and coiled states indicated by some studied order parameters is related to the definition of the order parameter and depends on the chain length of the polymer.Below the equilibrium melting temperature the (largest principal component of the) radius of gyration and the equilibrium lamellar thickness of the folded chain crystal decrease with increasing temperature, which gives support to the theory of Muthukumar but is opposite to the prediction of classical crystallization theories. The agreement between simulations and theory may hint to universal behavior of the relative equilibrium thickness versus the relative super cooling.

Structural and Computational Characterization of the SHV-1 β-Lactamase-β-Lactamase Inhibitor Protein Interface

Beta-lactamase inhibitor protein (BLIP) binds a variety of class A beta-lactamases with affinities ranging from micromolar to picomolar. Whereas the TEM-1 and SHV-1 beta-lactamases are almost structurally identical, BLIP binds TEM-1 approximately 1000-fold tighter than SHV-1. Determining the underlying source of this affinity difference is important for understanding the molecular basis of beta-lactamase inhibition and mechanisms of protein-protein interface specificity and affinity. Here we present the 1.6A resolution crystal structure of SHV-1.BLIP. In addition, a point mutation was identified, SHV D104E, that increases SHV.BLIP binding affinity from micromolar to nanomolar. Comparison of the SHV-1.BLIP structure with the published TEM-1.BLIP structure suggests that the increased volume of Glu-104 stabilizes a key binding loop in the interface. Solution of the 1.8A SHV D104K.BLIP crystal structure identifies a novel conformation in which this binding loop is removed from the interface. Using these structural data, we evaluated the ability of EGAD, a program developed for computational protein design, to calculate changes in the stability of mutant beta-lactamase.BLIP complexes. Changes in binding affinity were calculated within an error of 1.6 kcal/mol of the experimental values for 112 mutations at the TEM-1.BLIP interface and within an error of 2.2 kcal/mol for 24 mutations at the SHV-1.BLIP interface. The reasonable success of EGAD in predicting changes in interface stability is a promising step toward understanding the stability of the beta-lactamase.BLIP complexes and computationally assisted design of tight binding BLIP variants.

Calculating proton uptake/release and binding free energy taking into account ionization and conformation changes induced by protein-inhibitor association: application to plasmepsin, cathepsin D and endothiapepsin-pepstatin complexes.

The protein-inhibitor binding energies of enzymes are often pH dependent, and binding induces either proton uptake or proton release. The proton uptake/release and the binding energy for three complexes with available experimental data were numerically studied: pepstatin-cathepsin D, pepstatin-plasmepsin II and pepstatin-endothiapepsin. Very good agreement with the experimental data was achieved when conformational changes were taken into account. The role of the desolvation energy and the conformational changes was revealed by modeling the complex, the separated molecules in the complex conformation and the free molecules. It was shown that the conformational changes induced by the complex formation are as important for the proton transfer as the loss of solvation energy caused by the burial of interface residues. The residues responsible for the proton transfer were identified and their contribution to the proton uptake/release calculated. These residues were found to be scattered along the whole protein rather than being localized only at the active site. In the case of cathepsin D, these residues were found to be highly conserved among the cathepsin D sequences of other species. It was shown that conformation and ionization changes induced by the complex formation are critical for the correct calculation of the binding energy. Taking into account the electrostatics and the van der Waals (vdW) energies within the Boltzmann distribution of energies and allowing ionization and conformation changes to occur makes the calculated binding energy more realistic and closer to the experimental value. The interplay between electrostatic and vdW forces makes the pH dependence of the binding energy smoother, because the vdW force acts in reaction to the changes of the electrostatic energy. It was found that a small fraction of the ionizable groups remain uncharged in both the free and complexed molecules. The sequence and structural position of these groups aligns well within the three proteases, suggesting that these may have specific role.

Interaction Energy in Polymer Blends Containing N-1-Alkylitaconamic Acids Moiety

Analysis of the interaction energy of N-1-alkylitaconamic acids to explain the miscibility behavior of polymers containing this moiety is performed. In order to calculate the interaction energy, many conformations of the N-1-alkylitaconamic acid fragments containing ethyl, propyl, butyl, hexyl, octyl, decyl, and dodecyl were selected randomly from molecular dynamic simulations. It was assumed that miscibility and other properties are determined by the enthalpy of mixing, ΔHmix, that ΔHmix is dominated by the local interactions between segments of the polymer chains, and, furthermore, that PΔVmix contribution can be ignored. The polymer miscibility is discussed by using interaction energies calculated from molecular mechanics studies on pairs of small polymer fragments. By this method and by using the Blend package (Accelrys), good correlations between the interaction energy and the Gordon Taylor constant (KGT) values for blends of poly(N-1-alkylitaconamic acids) and poly(4-vinylpyridine) previously reported are obtained. The analysis of the energies shows that Coulombic energies decay rapidly being almost “zero” as the side-chain lengths reach near eight carbon atoms. On the contrary, the van der Waals interaction (VDW) energies decay in a linear way as the length of the side chain increases. The slope of the VDW energies is an estimation of the energetic contribution per methylene unit to the blending process. The slope in this case is 570 cal/mol, which is a value very close to that experimentally reported in the literature for related systems. The blend energy was calculated, and good correlation with the experimental results is obtained.

Prospects for a van der Waals density functional

The van der Waals (vdW) or dispersion interaction between distant sections of a molecular or condensed matter system contributes part of the correlation energy. This dispersion part is missed, or is given at best unreliably, by the usual local and gradient functionals for the exchange–correlation energy. Here we discuss various quasi-local schemes which are expected to provide good vdW energies using only a knowledge of the ground-state electron density n(r). The general scheme proposed is “seamless,” i.e., it remains valid whether or not the subsystems involved have significant overlap of electronic density. Perturbative expansion of this scheme, followed by a doubly local density approximation, yields a simple vdW scheme proposed independently by Andersson et al. and by Dobson and Dinte, which is also similar to a scheme of Rapcewicz and Ashcroft. These simpler schemes cannot deal with overlap between the electron clouds. Progress is reported on the full seamless scheme which deals with the more challenging case where overlap is present. All of the present schemes yield the classic dipolar “van der Waals” 1/R6 energy when the separation R sufficiently exceeds the individual system dimensions. None is restricted to this case, however. © 1998 John Wiley & Sons, Inc. Int J Quant Chem 69: 615–618, 1998

Toward the correct calculation of van der Waals interactions between lyophobic colloids in an aqueous medium

Abstract We have developed an accurate and simple method for calculating van der Waals (vdw) forces in condensed media based on the Lifshitz theory and have generalized that theory to apply to the interaction of two planar parallel lipid slabs in an aqueous medium. Several features of vdw forces in lipid-water systems are qualitatively different from the common assumptions of colloid science: (1) vdw energies are not the sum of ( λ / r 6 ) interactions between small elements of the interacting bodies; (2) electromagnetic fluctuations at ultraviolet frequencies, usually considered exclusively, are relatively unimportant compared to fluctuations at infrared and microwave frequencies; (3) by virtue of the strong microwave contribution, vdw forces in lipid-water mixtures increase with temperature and exhibit only weak “retardation” effects. Available spectral information is sufficient to derive these conclusions with little ambiguity. In particular, the feature of nonadditivity (which makes even the algebraic form of the interaction different from that expected) depends primarily on dielectric constants of component materials in the limit of zero frequency. Lifshitz' approach is conceptually clear. It correctly accounts for all frequencies of interaction, implicitly includes all many-body effects, and all consequences of intermediate substances. There is now good reason to use it in practice to calculate vdw forces for colloids at large separation distances.