Der Waals Energy Research Articles

Optimization of chromatographic separation of aripiprazole and impurities: Quantitative structure-retention relationship approach

A new optimization strategy based on the mixed quantitative structure? retention relationship (QSRR) model is proposed for improving the RPHPLC separation of aripiprazole and its impurities (IMP A-E). Firstly, experimental parameters (EPs), namely mobile phase composition and flow rate, were varied according to Box?Behnken design and thereafter, an artificial neural network (ANN) as a QSRR model was built correlating EPs and selected molecular descriptors (ovality, torsion energy and non-1,4-van der Waals energy) with the log-transformed retention times of the analytes. Values of the root mean square error (RMSE) were used for an estimation of the quality of the ANNs (0.0227, 0.0191 and 0.0230 for the training, verification and test set, respectively). The separations of critical peak pairs on chromatogram (IMP AB and IMP D-C) were optimized using ANNs for which the EPs served as inputs and the log-transformed separation criteria s as the outputs. They were validated by application of leave-one-out cross-validation (RMSE values 0.065 and 0.056, respectively). The obtained ANNs were used for plotting response surfaces upon which the analyses chromatographic conditions resulting in optimal analytes retention behaviour and the optimal values of the separation criteria s were defined. The optimal conditions were 54 % of methanol at the beginning and 79 % of methanol at the end of gradient elution programme with a mobile phase flow rate of 460 ?L min-1.

An integrated computational framework to design a multi-epitopes vaccine against Mycobacterium tuberculosis

Tuberculosis (TB) is a highly contagious disease that mostly affects the lungs and is caused by a bacterial pathogen, Mycobacterium tuberculosis. The associated mortality rate of TB is much higher compared to any other disease and the situation is more worrisome by the rapid emergence of drug resistant strains. Bacillus Calmette–Guerin (BCG) is the only licensed attenuated vaccine available for use in humans however, many countries have stopped its use as it fails to confer protective immunity. Therefore, urgent efforts are required to identify new and safe vaccine candidates that are not only provide high immune protection but also have broad spectrum applicability. Considering this, herein, I performed an extensive computational vaccine analysis to investigate 200 complete sequenced genomes of M. tuberculosis to identify core vaccine candidates that harbor safe, antigenic, non-toxic, and non-allergic epitopes. To overcome literature reported limitations of epitope-based vaccines, I carried out additional analysis by designing a multi-epitopes vaccine to achieve maximum protective immunity as well as to make experimental follow up studies easy by selecting a vaccine that can be easily analyzed because of its favorable physiochemical profile. Based on these analyses, I identified two potential vaccine proteins that fulfill all required vaccine properties. These two vaccine proteins are diacylglycerol acyltransferase and ESAT-6-like protein. Epitopes: DSGGYNANS from diacylglycerol acyltransferase and AGVQYSRAD, ADEEQQQAL, and VSRADEEQQ from ESAT-6-like protein were found to cover all necessary parameters and thus used in a multi-epitope vaccine construct. The designed vaccine is depicting a high binding affinity for different immune receptors and shows stable dynamics and rigorous van der Waals and electrostatic binding energies. The vaccine also simulates profound primary, secondary, tertiary immunoglobulin production as well as high interleukins and interferons count. In summary, the designed vaccine is ideal to be evaluated experimentally to decipher its real biological efficacy in controlling drug resistant infections of M. tuberculosis.

Role of electromagnetic fluctuations in organic electronics

Thin organic films find expanding applications in electronic and optoelectronic devices, biotechnology, food packing, and for many other purposes. Among other factors, the stability of films with a thickness below a micrometer is determined by the zero-point and thermal fluctuations of the electromagnetic field. These fluctuations result in the van der Waals and Casimir free energy and forces between a film and a substrate. The fluctuation-induced force may be both attractive and repulsive making the film either more or less stable, respectively. Here, we review recently obtained results for the Casimir free energy of both freestanding and deposited on the metallic and dielectric substrates peptide films. We also perform computations for the free energy of the peptide films deposited on a silica glass substrate in the region of parameters where this free energy vanishes. Possible applications of the obtained results are discussed.

Small protein–protein interfaces rich in electrostatic are often linked to regulatory function

Protein–protein interaction (PPI) is critical for several biological functions in living cells through the formation of an interface. Therefore, it is of interest to characterize protein–protein interfaces using an updated non-redundant structural dataset of 2557 homo (identical subunits) and 393 hetero (different subunits) dimer protein complexes determined by X-ray crystallography. We analyzed the interfaces using van der Waals (vdW), hydrogen bonding and electrostatic energies. Results show that on average homo and hetero interfaces are similar. Hence, we further grouped the 2950 interfaces based on percentage vdW to total energies into dominant (≥60%) and sub-dominant (<60%) vdW interfaces. Majority (92%) of interfaces have dominant vdW energy with large interface size (146 ± 87 (homo) and 137 ± 76 (hetero) residues) and interface area (1622 ± 1135 Å2 (homo) and 1579 ± 1060 Å2 (hetero)). However, a proportion (8%) of interfaces have sub-dominant vdW energy with small interface size (85 ± 46 (homo) and 88 ± 36 (hetero) residues) and interface area (823 ± 538 Å2 (homo) and 881 ± 377 Å2 (hetero)). It is found that large interfaces have two-fold more interface area and interface size than small interfaces with increasing hydrogen bonding energy to interface size. However, small interfaces have three-fold more electrostatics energy than large interfaces with increasing electrostatics to interface size. Thus, 8% of complexes having small interfaces with limited interface area and sub-dominant vdW energy are rich in electrostatics. It is interesting to observe that complexes having small interfaces are often associated with regulatory function. Hence, the observed structural features with known molecular function provide insights for the better understanding of PPI.Communicated by Ramaswamy H. Sarma

Molecular Modeling Approach to Investigate the Intercalation of Phthalates and Their Metabolites in DNA Macromolecules

Recent studies have reported that phthalates are capable of causing mutations and other changes in the genetic material. This study aimed to investigate the molecular interactions between phthalate di(2-ethylhexyl) phthalate (DEHP) and its metabolites monobutyl phthalate (MBP) and monoethyl phthalate (MEP), interacting with DNA. The research was conducted using molecular modeling techniques such as molecular docking and molecular dynamics simulations. Molecular docking revealed that the DEHP, MBP, and MEP are able to establish hydrogen interactions with various nucleotide bases. Molecular dynamics simulations revealed that these molecules interacted with the DNA, and the binding free energy results demonstrated that the DNA-ligand interaction has favorable free energy. The values for free binding energy were as follows: DNA–DEHP, –21.66 kcal/mol; DNA–MBP, –17.29 kcal/mol; and DNA–MEP, –20.13 kcal/mol. For these three systems, the contributions of van der Waals, electrostatic, and nonpolar solvation energy were favorable for the interaction. The van der Waals interactions contributed the major energy to the intercalation of the binders.

Exploring binding modes of the selected inhibitors to phosphodiesterase delta by all-atom molecular dynamics simulations and free energy calculations

It’s favorable to alter KRas mutation’s location to endomembrane by interfering the binding of PDEδ (the prenyl-binding protein phosphodiesterase delta) to KRas. In the present work, the binding of four inhibitors (Deltarasin, allyl analogue, pyrazolopyridazinone derivative, and Deltazinone 1) to PDEδ is investigated with all-atom Molecular Dynamic (MD) simulations. The binding free energy calculation results reveal that van der Waals (VDW) energy provides the major force for affinity binding. Moreover, the binding energy decomposition indicates that residues R61 and I129 provide important contributions to binding energies in all systems. The conserved hydrogen bonds play crucial roles in anchoring the inhibitors to the exact site for binding. The results for conformational analysis of PDEδ/free and PDEδ/inhibitors systems show that the structures are more stable after the inhibitors’ binding to the PDEδ. It is also found that the most unstable system among four complexes is PDEδ/pyrazolopyridazinone derivative system whose α3-helix formed by the residues P113-Q116 disappears. This study may provide valuable information for the design of high potency PDEδ inhibitors.Communicated by Ramaswamy H. Sarma

An explorative study on Staphylococcus aureus MurE inhibitor: induced fit docking, binding free energy calculation, and molecular dynamics

Staphylococcus aureus MurE enzyme catalyzes the addition of l-lysine as third residue of the peptidoglycan peptide moiety. Due to the high substrate specificity and its ubiquitous nature among bacteria, MurE enzyme is considered as one of the potential target for the development of new therapeutic agents. In the present work, induced fit docking (IFD), binding free energy calculation, and molecular dynamics (MD) simulation were carried out to elucidate the inhibition potential of 2-thioxothiazolidin-4-one based inhibitor 1 against S. aureus MurE enzyme. The inhibitor 1 formed majority of hydrogen bonds with the central domain residues Asn151, Thr152, Ser180, Arg187, and Lys219. Binding free-energy calculation by MM-GBSA approach showed that van der Waals (ΔGvdW, −57.30 kcal/mol) and electrostatic solvation (ΔGsolv, −36.86 kcal/mol) energy terms are major contributors for the inhibitor binding. Further, 30-ns MD simulation was performed to validate the stability of ligand–protein complex and also to get structural insight into mode of binding. Based on the IFD and MD simulation results, we designed four new compounds D1–D4 with promising binding affinity for the S. aureus MurE enzyme. The designed compounds were subjected to the extra-precision docking and binding free energy was calculated for complexes. Further, a 30-ns MD simulation was performed for D1/4C13 complex.

Instabilities in carbon nanocone stacks

Possessing remarkable electronic, mechanical and optical properties, pristine single-walled carbon nanocones (CNCs) are envisioned here to be pulled-out co-axially from a nanocone stack. The process is simulated using molecular mechanics (MM) and dynamics (MD) employing MM3 and REBO + LJ potentials, respectively. During pulling-out, rim of the lowermost cone is constrained while the tip of the outermost cone is displaced axially from its equilibrium, quasi-statically in case of MM and by prescribing velocity of 0.1 Å/pico-sec in case of MD. During pulling-out, at a critical distance, the top cone abruptly breaks the axial symmetry with its wall deforming considerably outward. The source of this instability is building-up of compressive circumferential strain in the wall with increasing displacement; a competition between stretching and van der Waal's energy terms of the system. Interestingly, during reversal of the pulling-out process, the system is found to trace a different equilibrium path. Further, in a few-walled CNCs if the tip of the top-most cone is compressed from its equilibrium position, the stack inverts completely by breaking axial symmetry aided by snap-through buckling in segments of the periphery. Irrespective of apex angle, hydrogen passivation, temperature and potential used, the aforementioned observations are found to be intrinsic to the system.

Insight into the structural requirements of thiophene-3-carbonitriles-based MurF inhibitors by 3D-QSAR, molecular docking and molecular dynamics study

The discovery of clinically relevant inhibitors against MurF enzyme has proven to be a challenging task. In order to get further insight into the structural features required for the MurF inhibitory activity, we performed pharmacophore and atom-based three-dimensional quantitative structure–activity relationship studies for novel thiophene-3-carbonitriles based MurF inhibitors. The five-feature pharmacophore model was generated using 48 inhibitors having IC50 values ranging from 0.18 to 663 μm. The best-fitted model showed a higher coefficient of determination (R2 = 0.978), cross-validation coefficient (Q2 = 0.8835) and Pearson coefficient (0.9406) at four component partial least-squares factor. The model was validated with external data set and enrichment study. The effectiveness of the docking protocol was validated by docking the co-crystallized ligand into the catalytic pocket of MurF enzyme. Further, binding free energy calculated by the molecular mechanics generalized Born surface area approach showed that van der Waals and non-polar solvation energy terms are the main contributors to ligand binding in the active site of MurF enzyme. A 10-ns molecular dynamic simulation was performed to confirm the stability of the 3ZM6-ligand complex. Four new molecules are also designed as potent MurF inhibitors. These results provide insights regarding the development of novel MurF inhibitors with better binding affinity.

Deciphering the crucial residues involved in heterodimerization of Bak peptide and anti-apoptotic proteins for apoptosis

B-cell lymphoma 2 (Bcl-2) family proteins are the central regulators of apoptosis, functioning via mitochondrial outer membrane permeabilization. The family members are involved in several stages of apoptosis regulation. The overexpression of the anti-apoptotic proteins leads to several cancer pathological conditions. This overexpression is modulated or inhibited by heterodimerization of pro-apoptotic BH3 domain or BH3-only peptides to the hydrophobic groove present at the surface of anti-apoptotic proteins. Additionally, the heterodimerization displayed differences in binding affinity profile among the pro-apoptotic peptides binding to anti-apoptotic proteins. In light of discovering the novel peptide/drug molecules that contain the potential to inhibit specific anti-apoptotic protein, it is necessary to understand the molecular basis of recognition between the protein and its binding partner (peptide or ligand) along with its binding energies. Therefore, the present work focused on deciphering the molecular basis of recognition between pro-apoptotic Bak peptide binding to different anti-apoptotic (Bcl-xL, Bfl-1, Bcl-W, Mcl-1, and Bcl-2) proteins using advanced Molecular Dynamics (MD) approach such as Molecular Mechanics-Generalized Born Solvent Accessible. The results from our investigation revealed that the predicted binding free energies showed excellent correlation with the experimental values (r2 = .95). The electrostatic (ΔGele) contributions are the major component that drives the interaction between Bak peptides and different anti-apoptotic peptides. Additionally, van der Waals (ΔGvdw) energies also play an indispensible role in determining the binding free energy. Furthermore, the decomposition analysis highlighted the comprehensive information about the energy contributions of hotspot residues involved in stabilizing the interaction between Bak peptide and different anti-apoptotic proteins.

A Monte Carlo simulation study to predict the solubility of H2S in ionic liquids with 1-butyl-3-methylimidazolium ([C4mim+]) cation and tetrafluoroborate ([BF4−]), hexaflorophosphate ([PF6−]) and bis(trifluoromethanesulfonyl)amide ([Tf2N−]) anions

The solubilities of H2S in ionic liquids, 1-butyl-3-methylimidazolium tetrafluoroborate ([C4mim+][BF4−]), 1-butyl-3-methylimidazolium hexaflorophosphate ([C4mim+][PF6−]) and -butyl-3-methylimidazolium tetrafluoroborate bis(trifluoromethanesulphonyl)amide ([C4mim+][Tf2N−]) are predicted using isothermal–isobaric Gibbs ensemble Monte Carlo method (NPT-GEMC) at temperatures ranging from 333 to 453 K and pressure up to 20 bar. The low pressure points (up to 3 bar) of the absorption isotherms are fitted to a straight line to get a rough estimation of the Henry’s law constants. The van’t Hoff relationship is used to estimate the partial molar enthalpy of the absorption. The obtained results are in a good agreement with Jou and Mather [18], and Jalili et al. [13]. When comparing the solubility in ILs, it is found that H2S solubility is highest for [C4mim+][Tf2N−], followed by [C4mim+][PF6−]. The lowest solubility is observed in [C4mim+][BF4−]. The highest solubility in [C4mim+][Tf2N−] is consistent with Jalili et al. [13]. However, their results indicate slightly higher solubility in [C4mim+][BF4−] than in [C4mim+][PF6−], and do not agree with the predictions. Upon absorption, the molar volumes of the mixtures decrease linearly, showing only small changes in volume. The effect of H2S absorption on ILs is further studied by calculating the radial distribution functions between the ions. The results indicate that the solute molecules accommodate themselves in the cavities without significantly disturbing the ionic arrangement of the ions, similar to CO2 absorption in ILs. The spatial distribution functions show similar spatial distribution for H2S around cation in all of the studied ILs, whereas the distribution around anion depends on the shape and flexibility of the anion. The mechanism of H2S absorption is studied by computing the van der Waals (VDW) and electrostatic (ELEC) energies. It is observed that the solubility of H2S in the studied ILs is primarily controlled by VDW interaction. When comparing the interaction of H2S with the ions, it is found that solute molecules interact with cations mainly due to VDW interaction. Both VDW and ELEC energies contribute in the interaction between H2S and anions.

Particle Deposition and Removal of Relevance to Wet Processing in Semiconductor Manufacturing

Removal of particulate contaminants from surfaces is a critical area in the processing of wafers to build integrated circuits and is typically done using wet chemical formulations. Strategies for particle removal require an understanding of particle deposition mechanisms. In the first part of this review paper, colloid chemical principles underlying particle deposition on surfaces is discussed. Specifically, the importance of van der Waals and electrical double layer interaction energy on particle–surface interaction is reviewed. This is followed by a description of commonly used particle removal methods in wafer processing, viz., megasonic cleaning, brush cleaning, and nanospray cleaning. The importance of particle deposition conditions used in research on particle removal efficiency is highlighted through a study on the effect of aging.

Effect of T68A/N126Y mutations on the conformational and ligand binding landscape of Coxsackievirus B3 3C protease.

3C protease of Coxsackievirus B3 (CVB3) plays an essential role in the viral replication cycle, and therefore, emerged as an attractive therapeutic target for the treatment of human diseases caused by CVB3 infection. In this study, we report the first account of the molecular impact of the T68A/N126Y double mutant (Mutant(Bound)) using an integrated computational approach. Molecular dynamics simulation and post-dynamics binding free energy, principal component analysis (PCA), hydrogen bond occupancy, SASA, R(g) and RMSF confirm that T68A/N126Y instigated an increased conformational flexibility due to the loss of intra- and inter-molecular hydrogen bond interactions and other prominent binding forces, which led to a decreased protease grip on the ligand (3CPI). The double mutations triggered a distortion orientation of 3CPI in the active site and decreases the binding energy, ΔG(bind) (∼3 kcal mol(-1)), compared to the wild type (Wild(Bound)). The van der Waals and electrostatic energy contributions coming from residues 68 and 126 are lower for Mutant(Bound) when compared with Wild(Bound). In addition, variation in the overall enzyme motion as evident from the PCA, distorted hydrogen bonding network and loss of protein-ligand interactions resulted in a loss of inhibitor efficiency. The comprehensive molecular insight gained from this study should be of great importance in understanding the drug resistance against CVB3 3C protease; also, it will assist in the designing of novel Coxsackievirus B3 inhibitors with high ligand efficacy on resistant strains.

Identification of Important Residues by Computational Alanine Scanning Analysis of Interaction Mechanisms of scFv Anti-p17 Complexes Based on Molecular Dynamics Simulations

Molecular dynamics simulation (MD) coupled with molecular mechanics generalized Born surface area (MM-GBSA) method were performed to probe the binding mechanisms of single chain Fv fragment with p17 epitopes of HIV-1 protease (scFv anti-p17). The results show that van der Waals and electrostatic energy is a main force of the binding. Computational alanine scanning by substitution of the amino acids in binding to alanine and analysis of structure-affinity relation were used to predict the antibody-antigen binding modes. The important residues locate in the hot spot of the surface between scFv and p17 have been identified. This study can contribute significantly to the designs of the novel antibody targeting the p17 peptides. Point mutations and molecular docking between the modeled scFv antibody and p17 peptides have been investigated in some of the key residues to search for novel antibody with the improved binding activity. The experimental results have been compared to see how well of the prediction.

Computational evaluation of new homologous down regulators of translationally controlled tumor protein (TCTP) targeted for tumor reversion

The Translationally Controlled Tumor Protein (TCTP) has been investigated for tumor reversion and is a target of cancer therapy. Down regulators which suppress the expression of TCTP can trigger the process of tumor reversion leading to the transformation of tumor cells into revertant cells. The present investigation is a novel protein-protein docking approach to target TCTP by a set of proteins similar to the protein: sorting nexin 6 (SNX6) which is an established down regulator of TCTP. The established down regulator along with its set of most similar proteins were modeled using the PYTHON based software - MODELLER v9.9, followed by structure validation using the Procheck Package. Further TCTP was docked with its established and prospective down regulators using the flexible docking protocol suite HADDOCK. The results were evaluated and ranked according to the RMSD values of the complex and the HADDOCK score, which is a weighted sum of van der Waal's energy, electrostatic energy, restraints violation energy and desolvation energy. Results concluded the protein sorting nexin 6 of Mus musculus to be a better down regulator of TCTP, as compared to the suggested down regulator (Homo sapiens snx6).

Prediction of estrogen receptor β ligands potency and selectivity by docking and MM-GBSA scoring methods using three different scaffolds

This study aimed to identify the docking and molecular mechanics-generalized born surface area (MM-GBSA) re-scoring parameters which can correlate the binding affinity and selectivity of the ligands towards oestrogen receptor β (ERβ). Three different series of ERβ ligands were used as dataset and the compounds were docked against ERβ (protein data bank (PDB) ID: 1QKM) using Glide and ArgusLab. Glide docking showed superior results when compared with ArgusLab. Docked poses were then rescored using Prime-MM-GBSA to calculate free energy binding. Correlations were made between observed activities of ERβ ligands with computationally predicted values from docking, binding energy parameters. ERβ ligands experimental binding affinity/selectivity did not correlate well with Glide and ArgusLab score. Whereas calculated Glide energy (coulomb-van der Waal interaction energy) correlated significantly with binding affinity of ERβ ligands (r2 = 0.66). MM-GBSA re-scoring showed correlation of r2 = 0.74 with selectivity of ERβ ligands. These results will aid the discovery of novel ERβ ligands with isoform selectivity.

Role of the Polar Properties of Water in Separation Methods

The role of the polar properties of water in separation methods are presented in two parts: Part I: Properties of Water General principles are given of the three non-covalent energy types acting upon non-polar as well as polar entities when these are immersed in water: Lifshitz-van der Waals (LW), Lewis Acid-Base (AB) and Electrostatic (EL) energies. The dominant one of these three is the Lewis acid-base (AB) interaction, which in biochemical and other organic interactions are about an order of magnitude stronger than the van der Waals and electrostatic energies combined. Included are the most important equations, describing these interactions when occurring in water. Part II: Forces Originating in Water and their Significance in Separation Methods • Hydrophobic attraction between particles. • Hydrophobic interaction between solute molecules immersed in liquid water is caused by the hydrogen-bonding free energy of cohesion between the water molecules which surround these particles or solute molecules. • The solubility equation is given, which links the free energy of interaction, ΔGiwi, between the solute molecules (i) immersed in water (w), and the natural logarithm of the aqueous solubility (s) of i, expressed in mol fractions. Insolubility and partial solubility in water are due to strong mutual attraction and moderate attraction among molecules, respectively. Total solubility in water is due to mutual repulsion between solute molecules. • Discusses conditions of stability versus instability (flocculation) of aqueous particle suspensions. • Discusses the hyper-hydrophobicity of the water-air interface and its interactions with: A) small water-soluble molecules (it repels them) and: (B) amphiphilic molecules such as surfactants, alcohols, proteins, etc. (it strongly attracts them). • Treats adhesion and adsorption energies between two different entities, immersed in water, such as antigens and antibodies. These energies are commonly expressed as affinity constants (Kaff), the value of which is strongly influenced by the time spent during the initial adhesion or adsorption step, where the Kaff value steadily increases the longer that initial adsorption step lasts. This phenomenon is called hysteresis, or binding hysteresis. However the hysteresis effect can be avoided by reducing the initial exposure episode to time (t) approaching t = 0, to obtain Kaff t→0. • Two different aqueous phases can be formed by dissolving two different water-soluble polymers, e.g., poly-(ethylene oxide) and dextran, which repel one another in aqueous solution. Such aqueous two-phase systems can be used cause the preferential migration of two different solutes to two different phases and thus to effect their separation and purification. Results of a study of multiple sub-phases forming within the middle phase of micro-emulsions are also discussed. • Advancing freezing fronts are discussed in this Section, i.e., the rejection or engulfment of certain solutes or cells by a vertical ice column which is made to advance further vertically by continuing to cool it from below. • The size, or rather the radius of curvature (R) of blood cells, blood proteins, bacteria and viruses, can play an important role in, e.g., the in vivo phagocytic engulfment of bacteria by leucocytes, the transformation of platelets to become “sticky”, the attachment of viruses to cells and of bacteriophages to bacteria.

IVGA3D: De Novo Ligand Design Using a Variable Sized Tree Representation

Rational drug design is an important step towards effective patient care enabling lead molecule discovery in a relatively faster and inexpensive way. This article describes a variable string length genetic algorithm with domain specific operators for de novo ligand design. The algorithm first mines the active site of the given protein receptor whose geometry and chemical composition guides the ligand building. Active site mined by the algorithm is compared with two more established active sites detecting schemes to evaluate its efficiency. Various combinations from a suite of forty one fragments are mined to design the ligands. Bond stretching, angle bending, torsional terms, van der Waals and electrostatic interaction energy with distance dependent dielectric constant contribute are used to compute the internal energy of the ligand and the interaction energy of the ligand receptor complex. Forty one fragments are used to design the ligands. Experimental results are provided for HIV-1 Protease, HIV-1 Nef and Thrombin demonstrating the superiority of the proposed scheme vis-a-vis three other approaches. Comparison with known inhibitors also demonstrates the effectiveness of the proposed approach.

Oligomer adsorption on dry and wet collagen surfaces

The development of new biodegradable polymeric tissue adhesives has been almost stagnant for the past 10 years, primarily due to the inability to overcome the problem of inadequate adhesion properties. Efforts at the synthesis and modification of chemical structures by incorporating functional groups have proven futile. This study proposes using simulation as a preliminary move to obtain a better understanding of adsorption behavior on biological tissues. It is hoped that this understanding will subsequently serve as a guide for better polymer design and synthesis. Adsorption under both dry and wet conditions were simulated applying classical molecular mechanics and dynamics (MM/MD) because of their relevancy and efficiency. Twelve types of oligomers and a model collagen surface were constructed, followed by structural optimization and equilibration treatments. The COMPASS force field was used to describe the molecular potential energy surfaces. One strand of the oligomer was then located on top of the collagen surface and their interactions at equilibrium, in terms of van der Waals (vdW) and electrostatic energies, monitored over time. For the wet environment a thick water layer was constructed and placed on top of the oligomer and collagen surface. The results showed that the vdW component dominated physical adsorption for all oligomers, under both dry and wet conditions. This implies that interactions of polymers with tissue surfaces are inherently weak. Functional groups on oligomers could improve adhesion via electrostatic interaction. This interaction is, however, screened off in a wet environment, resulting in a reduction in the adsorption energy for all molecules studied. Of all the oligomers studied, poly(glycine) showed the strongest adsorption to collagen in both dry and wet conditions. Therefore, it is proposed to include the functional groups present in poly(glycine) in future tissue adhesive systems.

Conformational energy calculations demonstrating the β turn and other secondary structural features in the repeat pentapeptide of elastin

Conformational energy of the repeat pentapeptide of elastin, N-formyl-L-Val-L-Pro-Gly-L-Val-Gly-OCH3, was determined as a function of backbone torsion angles ϕ and ψ. Total conformational energy was assumed to consist of van der Waals, electrostatic, torsional, and hydrogen bond energies. Electrostatic energy was calculated using ab initio minimal basis set (STO-3G) net charges. Major conformational features observed are a ten-membered hydrogen-bonded type II β-turn system involving Val1 C'O and Val4 NH and a seven-membered equatorial (C7eq) conformation involving Gly3 C'O and Gly5 NH. The β-turn conformation is dominantly stabilized by the hydrogen-bond energy. A limited interaction is observed between Gly5 C'O and Gly3 NH. These theoretical results are compared with proton and carbon-13 magnetic resonance studies of this laboratory.