Comparative study of stability and transport of molecules through cyclic peptide nanotube and aquaporin: a molecular dynamics simulation approach

Abstract

The structural stability and transport properties of the cyclic peptide nanotube (CPN) 8?×?[Cys–Gly–Met–Gly]₂ in different phospholipid bilayers such as POPA (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidic acid), POPE (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine), POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine), POPG (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol) and POPS (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoserine) with water have been investigated using molecular dynamics (MD) simulation. The hydrogen bonds and non-bonded interaction energies were calculated to study the stability in different bilayers. One µs MD simulation in POPA lipid membrane reveals the stability of the cyclic peptide nanotube, and the simulations at various temperatures manifest the higher stability of 8?×?[Cys–Gly–Met–Gly]₂. We demonstrated that the presence of sulphur-containing amino acids in CPN enhances the stability through disulphide bonds between the adjacent rings. Further, the water permeation coefficient of the CPN is calculated and compared with human aquaporin-2 (AQP2) channel protein. It is found that the coefficients are highly comparable to the AQP2 channel though the mechanism of water transport is not similar to AQP 2; the flow of water in the CPN is taking place as a two-line 1–2–1–2 file fashion. In addition to that, the transport behavior of Na⁺ and K⁺ ions, single water molecule, urea and anti-cancer drug fluorouracil were investigated using pulling simulation and potential of mean force calculation. The above transport behavior shows that Na⁺ is trapped in CPN for a longer time than other molecules. Also, the interactions of the ions and molecules in Cα and mid-Cα plane were studied to understand the transport behavior of the CPN. Abbreviations AQP2 Aquaporin-2

CPN Cyclic peptide nanotube

MD Molecular dynamics

POPA 1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphatidic acid

POPE 1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine

POPG 1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol

POPS 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoserine

Communicated by Ramaswamy H. Sarma     

Molecular simulation on the interaction of Ethinylestradiol (EE2) with polymer membranes in wastewater purification

Molecular dynamics (MD) simulations are performed to study the adsorption of solute organic molecules (Ethinylestradiol (EE2) and testosterone) with different polymer membranes such as polyether sulfone (PES), polyvinylidene fluoride (PVDF). The equilibrium MD simulations results for the membrane solution interface system show that the interaction of EE2 with PES is specific and strong, whereas the interaction is weak and non-specific for PVDF. The binding free energies, the non-bonded short range interaction energies and mobility are also consistent with the interaction behaviour found in experiments. The adsorption of testosterone onto PES and PVDF is considered as control system. The result shows that binding free energies of PES and PVDF interacting with organic solute are consistent with experimental result in the order as; PES-EE2 > PES-Testosterone > PVDF-EE2 > PVDF-Testosterone. The formation hydrogen bonds and π–π interactions are observed between the EE2 and PES. In addition, adsorption of EE2 onto polyamide 6-12 (PA612) and polystyrene (PS) membranes are predicted. This simulation study provides molecular insights on the experimental observations and helps as a computational methodology to screen the membrane materials for EE2 removal from wastewater.     

A theoretical study on the stability of CNT encased cyclic peptide beyond hydrogen bond cut-off

The Carbon nanotubes (CNT) are potential candidate for many biomedical applications especially in targeted drug delivery for cancer diseases. However, the use of CNT has limitations due to its insolubility in aqueous media. The self-assembly of cyclic peptide encased on the CNT has enhanced its dispersion in aqueous medium which extend their applications as antibacterial and drug delivery agents. To understand this process, an attempt has been made to investigate the dynamics and stability of trimer cyclic peptide encasing with CNT using classical molecular dynamics. The model cyclic peptide monomer constitutes 14 series of amino acids viz.; (cyclo-[(D-ARG-L-VAL-D-ARG-L-THR-D-AGR-L-LYS-D-GLY-L-ARG-D-ARG-L-ILE-D-ARG-L-ILE-D-PRO-L-PRO)]). Each cyclic peptide in the assembly stacking far apart at approximately 15 Å each other beyond hydrogen bond cut-off distance. The trimer was observed to be stable only over 10 ns of entire MD trajectory. But when there is electrostatic interaction between cyclic peptides at 6.5 Å distance then assembly is stable for entire 50 ns. Our result reveals that for a stable assembly, beyond the hydrogen bond cut-off distance, the electrostatic interaction plays significant role.     

A theoretical investigation on the conformation and the interaction of CHF2OCF2CHF2 (desflurane II) with one water molecule

The conformation and the interaction of CHF₂OCF₂CHF₂ (desflurane II) with one water molecule is investigated theoretically using the ab initio MP2/aug-cc-pvdz and DFT-based M062X/6-311++G(d,p) methods. The calculations include the optimized geometries, the harmonic frequencies of relevant vibrational modes along with a natural bond orbital (NBO) analysis including the NBO charges, the hybridization of the C atom and the intra- and intermolecular hyperconjugation energies. In the two most stable conformers, the CH bond of the F₂HCO- group occupies the gauche position. The hyperconjugation energies are about the same for both conformers and the conformational preference depends on the interaction between the non-bonded F and H atoms. The deprotonation enthalpies of the CH bonds are about the same for both conformers, the proton affinity of the less stable conformer being 3 kcal mol^?1 higher. Both conformers of desflurane II interact with water forming cyclic complexes characterized by CH…O and OH…F hydrogen bonds. The binding energies are moderate, ranging from ?2.4 to ?3.2 kcal mol^?1 at the MP2 level. The origin of the blue shifts of the ν(CH) vibrations is analyzed. In three of the complexes, the water molecule acts as an electron donor. Interestingly, in these cases a charge transfer is also directed to the non bonded OH group of the water molecule. This effect seems to be a property of polyfluorinated ethers.     

Combined theoretical studies on solvation and hydrogen bond interactions in glycine tripeptide

The theoretical conformational analysis of glycine tripeptide (GT) has been carried out by molecular dynamics (MD) method in order to find minimum energy conformations. The MD studies on GT with water have been carried out for over 10 ns with a time step of 2 fs using fixed charge force field (AMBER ff03). By adding the solvation effect using water as a solvent, the GT conformers identified in this study exhibit α-helical conformation. Compared with the earlier reports, this MD study is able to identify the energetically favourable GT conformations. The obtained geometry of the five most stable GT conformations was optimised using the density functional theory method at B3LYP/6-311G** level of theory. Subsequently, the effects of solvation on the conformational characteristics of five most stable GT conformers with four water molecules (the number of water molecules in the first solvation shell of GT obtained from MD study) were investigated using the same method and the same level of theory. The effect of microsolvation on the fifth GT conformer has been studied with a cluster of 11 water molecules as the first hydration shell which generates folded structure. The interaction energies of all the complexes are calculated by correcting the basis set superposition error. The strong hydrogen bond mainly contributes to the interaction energies. The atoms in molecules theory and natural bond orbital analysis were used to study the origin of H-bonds. A good correlation between the structural parameters and the properties of charge density is found. NMR calculations show that the C = O carbons of the amine groups of the first and middle glycine fragments have maximum chemical shifts.     

Free energy surface for rotamers of cis-enol malonaldehyde in aqueous solution studied by molecular dynamics calculations

Two-dimensional free energy surfaces for four rotamers of cis-enol malonaldehyde in water have been investigated by umbrella sampling molecular dynamics (MD) calculations. Biasing potential used in the umbrella sampling calculation was adopted to be the minus of conformational free energy preliminary obtained by the thermodynamic integration MD calculations for the rigid malonaldehyde whose stretching and bending were all fixed. The calculated free energy surface shows that, in water, a rotamer that has an intramolecular hydrogen bond is most stable among the rotamers. This is the same as that in vacuum, while order of relative stability of the other three rotamers is different in water and in vacuum. Inclusion of intramolecular vibrations changed the free energy surface little, i.e. at most 2.6 kJ/mol, which is much smaller than the solvation free energy. Free energy barriers from the most stable intramolecular hydrogen bonded rotamer to the others are lowered by hydration but they are still very high, >50 kJ/mol, such that the malonaldehyde molecule spends most of its time in water taking this conformation. Thus, reaction coordinate for intramolecular proton transfer reaction in water may be constructed assuming this rotamer.     

Computational modelling and molecular dynamics simulations of a cyclic peptide mimotope of the CD52 antigen complexed with CAMPATH-1H antibody

A peptide mimotope of the CD52 antigen with the sequence T₁SSPSAD₇ has been co-crystallised with the CAMPATH-1H antibody. Molecular dynamics (MD) simulations in explicit water of the T₁SSPSAD₇ peptide in both antibody free and bound states showed that the peptide's β-turn remained stable in the bound state but it was eliminated in the free state. Based on the observation that Thr₁ and Ala₆ residues made close contacts through their side chain, a new peptide mimotope is proposed: (S,S)-C₁SSPSCD₇. Thr₁ and Ala₆ residues have been mutated in Cys residues and a disulphide bond has been imposed. The new analogue has been simulated in both antibody bound and free states with MD in explicit water. It was found that the peptide remained in the stable β-turn conformation, both in complexed and free states. The difference in configurational entropy was estimated to be 0.15 kJ/K/mol. However, despite the structural similarity, the cyclic analogue lost more than 25% of its buried surface area contact with the antibody and a couple of critical hydrogen bond interactions were broken. It is concluded that design of cyclic analogues that mimic the bound conformation of peptides should be carefully performed and conformational ‘freezing’ does not necessarily guarantee better binding.     

Exploring the differences and similarities between urea and thermally driven denaturation of bovine serum albumin: intermolecular forces and solvation preferences

The interactions of bovine serum albumin (BSA) with urea/water were investigated by computer simulation. It was revealed that the BSA-hydrophobic residues in urea solutions favored contact with urea more than with water. Energy decomposition analysis showed that van der Waals energy was the dominant driving force behind urea affinity for hydrophobic residues, whereas coulombic attraction was largely responsible for water affinity for these residues. Meanwhile, urea–BSA hydrogen bond energies were found to be weaker than water–BSA hydrogen bond energies. The greater strength of water–BSA hydrogen bonds than urea–BSA hydrogen bonds, and the opposing preferential interaction between the BSA and urea suggest that disruption of hydrophobic interaction predominates urea–protein denaturation. In pure water, hydrophobic residues showed aggregation tendencies at 323 K, suggesting an increase in hydrophobicity, while at 353 K the residues were partly denatured due to loss of hydrogen bonds; thus, disruption of hydrophobic interactions appeared to contribute less to thermal denaturation.     

Effects of hypochlorous acid on unsaturated phosphatidylcholines.

Effects of hypochlorous acid and of the myeloperoxidase-hydrogen peroxide-chloride system on mono- and polyunsaturated phosphatidylcholines were analyzed by means of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Chlorohydrins and glycols were detected as main products according to the characteristic shift of molecular masses. Mainly mono-chlorohydrins result upon the incubation of HOCl/(-)OCl with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, whereas only traces of mono-glycols were detected. 1-Palmitoyl-2-linoleoyl-sn-glycero-3-phosphocholine yielded a complex mixture of products. Mono-chlorohydrins and glycols dominated only at short incubation, while bis-chlorohydrins as well as products containing one chlorohydrin and one glycol moiety appeared after longer incubation. Similarly, a complex product mixture resulted upon incubation of 1-stearoyl-2-arachidonoyl-sn-glycero-3-phosphocholine with hypochlorous acid. Additionally, tris-chlorohydrins, products with two chlorohydrin and one glycol moiety, as well as lysophosphatidylcholines and fragmentation products of the arachidonoyl side chain were detectable. Mono-chlorohydrins of 1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine were detected after the incubation of the latter phospholipid with the myeloperoxidase-hydrogen peroxide-chloride system at pH 6.0. These chlorohydrins were not observed in the absence of chloride, hydrogen peroxide, or myeloperoxidase as well as in the presence of methionine, taurine, or sodium azide. Thus, mono-chlorohydrins in 1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine produced by hypochlorous acid from the myeloperoxidase-hydrogen peroxide-chloride system can also be detected by means of MALDI-TOF MS.     

Competition and interplay between the lithium bonding and hydrogen bonding: R3C···HY···LiY and R3C···LiY···HY triads as a working model (R=H, CH3; Y=CN, NC)

UMP2 calculations with aug-cc-pVDZ basis set were used to analyze intermolecular interactions in R₃C···HY···LiY and R₃C···LiY···HY triads (R=H, CH₃; Y=CN, NC), which are connected via lithium and hydrogen bonds. To better understand the properties of these systems, the corresponding dyads were also studied. Molecular geometries and binding energies of dyads, and triads were investigated at the UMP2/aug-cc-pVDZ computational level. Particular attention was paid to parameters such as cooperative energies, and many-body interaction energies. All studied complexes, with the simultaneous presence of a lithium bond and a hydrogen bond, showed cooperativity with energy values ranging between ?1.71 and ?9.03 kJ mol^?1. The electronic properties of the complexes were analyzed using parameters derived from atoms in molecules (AIM) methodology. Energy decomposition analysis revealed that the electrostatic interactions are the major source of the attraction in the title complexes.     

Probing the interaction between cHAVc3 peptide and the EC1 domain of E-cadherin using NMR and molecular dynamics simulations

The goal of this work is to probe the interaction between cyclic cHAVc3 peptide and the EC1 domain of human E-cadherin protein. Cyclic cHAVc3 peptide (cyclo(1,6)Ac-CSHAVC-NH₂) binds to the EC1 domain as shown by chemical shift perturbations in the 2D ¹H,-¹⁵N-HSQC NMR spectrum. The molecular dynamics (MD) simulations of the EC1 domain showed folding of the C-terminal tail region into the main head region of the EC1 domain. For cHAVc3 peptide, replica exchange molecular dynamics (REMD) simulations generated five structural clusters of cHAVc3 peptide. Representative structures of cHAVc3 and the EC1 structure from MD simulations were used in molecular docking experiments with NMR constraints to determine the binding site of the peptide on EC1. The results suggest that cHAVc3 binds to EC1 around residues Y36, S37, I38, I53, F77, S78, H79, and I94. The dissociation constants (K_d values) of cHAVc3 peptide to EC1 were estimated using the NMR chemical shifts data and the estimated K_ds are in the range of .5 × 10^?5–7.0 × 10^?5 M.     

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 (ΔG_ele) contributions are the major component that drives the interaction between Bak peptides and different anti-apoptotic peptides. Additionally, van der Waals (ΔG_vdw) 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.     

Investigation and optimisation of the drying of reduced glutathione by steered molecular dynamics simulation

The drying of reduced glutathione from a series of aqueous–ethanol binary solutions at 300 K (below human body temperature) and 330 K (above human body temperature) was investigated in detail by steered molecular simulation and an umbrella sampling method with the Gromacs software package and Gromos96(53a6) united atomic force field. The results show that electrostatic interactions between glutathione and solvent represent the main resistance to drying. When the aqueous solution was gradually changed to pure ethanol, the energy of electrostatic interaction between glutathione and solvent molecules increased by 445.088 kJ/mol, and the drying potential of mean force (PMF) free energy also fell by 253.040 kJ/mol. However, an increase in temperature from 300 to 330 K in the aqueous solution only results in an increase of 23.013 kJ/mol in electrostatic interaction energy and a decrease of 34.956 kJ/mol in drying PMF free energy. Furthermore, we show that hydrogen bonding is the major form of electrostatic interaction involved, and directly affects the drying of glutathione. Therefore, choosing water-miscible solvents that minimise hydrogen-bond formation with glutathione will enhance its drying rate, and this is likely to be more efficient than increasing the temperature of the process. Thus, a power-saving technology can be used to produce the high bioactivity medicines.     

Free energy of helical transmembrane peptide dimerization in OPLS-AA/Berger force field simulations: inaccuracy and implications for partner-specific Lennard-Jones parameters between peptides and lipids

Interactions between transmembrane (TM) peptides are important in biophysical chemistry, but there are few studies assessing atomistic simulation parameters concerning the energetics of interactions of TM helical peptides. Our potential of mean force analysis using OPLS-AA protein/Berger lipid force fields (FFs) shows that the dimerisation energy of (AALALAA)₃ helical peptides in the dioleoylphosphatidylcholine bilayer is ?4.4 kJ/mol, which was much smaller than the reported experimental value (?12.7 kJ/mol), thus calling for improvement of parameters of the combined FFs. As each of the FFs has been independently developed, we then tested the effects of downscaling the Lennard-Jones (LJ) energy terms between the OPLS-AA atoms and Berger lipid atoms, preserving the parameters within each FF. A 0.9-fold rescaling of the LJ energies was found to render the dimerisation energy close to the experimental value. Solvation of backbone atoms as well as side chain atoms in lipids is crucial for the TM helix interaction. In similar analyses, GROMOS 53A6 FF exhibited as weak dimerisation propensity (~?5.2 kJ/mol) as OPLS-AA/Berger, but CHARMM36 showed relatively accurate propensity (~?9.9 kJ/mol). Challenges and strategies in rendering the TM interaction energy realistic within the framework of current FFs are discussed.     

Lipid bilayer molecular dynamics study of lipid-derived agonists of the putative cannabinoid receptor, GPR55

Both L-α-lysophosphatidylinositol (LPI) and 2-arachidonoyl-sn-glycero-3-phosphoinositol (2-AGPI) have been reported to activate the putative cannabinoid receptor, GPR55. Recent microsecond time-scale molecular dynamics (MD) simulations and isothiocyanate covalent labeling studies have suggested that a transmembrane helix 6/7 (TMH6/7) lipid pathway for ligand entry may be necessary for interaction with cannabinoid receptors. Because LPI and 2-AGPI are lipid-derived ligands, conformations that each assumes in the lipid bilayer are therefore likely important for their interaction with GPR55. We report here the results of 70 ns NAMD molecular dynamics (MD) simulations of LPI and of 2-AGPI in a fully hydrated bilayer of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC). These simulations are compared with a 70 ns simulation of the cannabinoid CB1 receptor endogenous ligand, N-arachidonoylethanolamine (anandamide, AEA) in a POPC bilayer. These simulations revealed that (1) LPI and 2-AGPI sit much higher in the bilayer than AEA, with inositol headgroups that can at times be solvated completely by water; (2) the behavior of the acyl chains of AEA and 2-AGPI are similar in their flexibilities in the bilayer, while the acyl chain of LPI has reduced flexibility; and (3) both 2-AGPI and LPI can adopt a tilted headgroup orientation by hydrogen bonding to the phospholipid phosphate/glycerol groups or via intramolecular hydrogen bonding. This tilted head group conformation (which represents over 40% of the conformer population of LPI (42.2 ± 3.3%) and 2-AGPI (43.7 ± 1.4%)) may provide a low enough profile in the lipid bilayer for LPI and 2-AGPI to enter GPR55 via the putative TMH6/7 entry port.     

Dipolar solvent relaxation on a nanosecond time scale in ether phospholipid membranes as determined by multifrequency phase and modulation fluorometry

The present study reports on the observation of dipolar solvent relaxation in phospholipid membranes using multifrequency phase and modulation fluorometry. We measured the time-resolved emission spectra of 6-propionyl-2-(dimethylamino)naphthalene (PRODAN) in artificial bilayer membranes of chemically defined acyl-, alkyl-, and alkenyl-substituted phospholipids at 15 degrees C. 1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, 3-O-hexadecyl-2-oleoyl-sn-glycero-1-phosphocholine, or 1-O-hexadec-1'-enyl-2-oleoyl-sn-glycero-3-phosphocholine (plasmalogen) were used as matrix lipids. The chemical structures of these lipids differ only with respect to the type of linkage (carboxyl ester, ether, or enol ether bond) between glycerol and the hydrophobic chain linked to the primary hydroxyl of glycerol. At 15 degrees C, all the lipids are in the liquid crystalline state. PRODAN probably localizes at the hydrophobic-hydrophilic interface of the phospholipid bilayer [Chong, P. L. (1988) Biochemistry 27, 399-404]. We found faster solvent relaxation of PRODAN in membranes composed of the ether lipid compared to that in the ester lipid membranes. On the other hand, the fluorescence anisotropies of the label were very similar, showing that the motion of the label itself is similar in ether and carboxyl ester lipids. We conclude that the spectral differences observed for PRODAN in ether and ester lipids could be due to different dipolar relaxation of the immediate surroundings of the label, i.e., reorientation of lipid dipoles in the glycerol region and of water molecules residing therein.     

Computer simulation of the interaction of α3hclix of λ Cro protein with DNA and origin of sequence specific recognition

The conformation of the α3 helix of Cro protein (residues 27–36) of bacteriophageλ is optimised by the damped least square minimization technique, with the steric constraint that Cα atom positions should match the crystallographic data available to date. On the basis of minimization of total interaction and conformation energy, models for complexes of this peptide sequence with heptanucleotide duplexes from native and altered O_R3 operator are obtained in the major groove of B DNA. Analysis of the energetics for 3 sequences of the DNA show that binding strength is derived mainly from the interaction of side chains of the peptide with DNA. Sequence specificity (maximum difference in binding energy for different DNA sequences) is due to hydrogen bonding interaction. A small amount of sequence specificity is derived from non-bonded interaction also. Stereochemical aspects of peptide DNA interaction and their role in DNA recognition are discussed in this paper.     

A semi-microscopic Monte Carlo study of permeation energetics in a gramicidin-like channel: the origin of cation selectivity.

The influence of a gramicidin-like channel former on ion free energy barriers is studied using Monte Carlo simulation. The model explicitly describes the ion, the water dipoles, and the peptide carbonyls; the remaining degrees of freedom, bulk electrolyte, non-polar lipid and peptide regions, and electronic (high frequency) permittivity, are treated in continuum terms. Contributions of the channel waters and peptide COs are studied both separately and collectively. We found that if constrained to their original orientations, the COs substantially increase the cationic permeation free energy; with or without water present, CO reorientation is crucial for ion-CO interaction to lower cation free energy barriers; the translocation free energy profiles for potassium-, rubidium-, and cesium-like cations exhibit no broad barriers; the lipid-bound peptide interacts more effectively with anions than cations; anionic translocation free energy profiles exhibit well defined maxima. Using experimental data to estimate transfer free energies of ions and water from bulk electrolyte to a non-polar dielectric (continuum lipid), we found reasonable ion permeation profiles; cations bind and permeate, whereas anions cannot enter the channel. Cation selectivity arises because, for ions of the same size and charge, anions bind hydration water more strongly.     

Effects of boron doping on structural,electronic, elastic,and optical properties of energetic crystal 2,6-diamino-3,5-dinitropyrazine-1-oxide: a theoretical study using the first principles calculation and Hirshfeld surface analysis

The activation or functionalization of the saturated C-H is an extremely active field at present. We have explored the triplet state thioxanthone in reactivity of the hydrogen transfer reaction between donors and acceptors. In our works, two donors with quasi-inert sp3 C-H of skipped diene (3,6-nonadiene) and cyclic acetals (benzodioxole) reacted with type II photoinitiators (triplet state of thioxanthone series, TXs) as acceptors are investigated. The excited energies of TXs were obtained by time-dependent density functional theory (TD-DFT). TXs show obvious photosensibility based on their low reorganization energies (< 60 kcal mol−1). The isoentropy reactions had linear geometries of transition state (TS). The distortion/interaction model was used to probe the existence of interaction between acceptors and donors in saddle point. The distortion energy and activation barrier of benzodioxole are much higher than those of the corresponding 3,6-nonadiene. The lower bond dissociation energy noticeably affect the transition state. The reaction of triplet state of TXs with skipped dienes were found to have an anomalous low tunneling factors by using Wigner correction and early transition state by using the bond-energy–bond-order method. The triplet state of TXs photoinitiator can induced the hydrogen abstraction from saturated cyclic acetals and the skipped alkadienes. The hydrogen abstraction experiment are confirmed by UV and real-time FTIR.     

Isothermal titration calorimetry studies of the binding of a rationally designed analogue of the antimicrobial peptide gramicidin s to phospholipid bilayer membranes

The binding of the positively charged antimicrobial peptide cyclo[VKLdKVdYPLKVKLdYP] (GS14dK4) to various lipid bilayer model membranes was investigated using isothermal titration calorimetry. GS14dK4 is a diastereomeric lysine ring-size analogue of the naturally occurring antimicrobial peptide gramicidin S which exhibits enhanced antimicrobial and markedly reduced hemolytic activities compared with GS itself. Large unilamellar vesicles composed of various zwitterionic (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphorylcholine [POPC]) and anionic phospholipids {1-palmitoyl-2-oleoyl-sn-glycero-3-[phospho-rac-(glycerol)] [POPG] and 1-palmitoyl-2-oleoyl-sn-glycero-3-[phosphoserine] [POPS]}, with or without cholesterol, were used as model membrane systems. Dynamic light scattering results indicate the absence of any peptide-induced major alteration in vesicle size or vesicle fusion under our experimental conditions. The binding of GS14dK4 is significantly influenced by the surface charge density of the phospholipid bilayer and by the presence of cholesterol. Specifically, a significant reduction in the degree of binding occurs when three-fourths of the anionic lipid molecules are replaced with zwitterionic POPC molecules. No measurable binding occurs to cholesterol-containing zwitterionic vesicles, and a dramatic drop in binding is observed in the cholesterol-containing anionic POPG and POPS membranes, indicating that the presence of cholesterol markedly reduces the affinity of this peptide for phospholipid bilayers. The binding isotherms can be described quantitatively by a one-site binding model. The measured endothermic binding enthalpy (DeltaH) varies dramatically (+6.3 to +26.5 kcal/mol) and appears to be inversely related to the order of the phospholipid bilayer system. However, the negative free energy (DeltaG) of binding remains relatively constant (-8.5 to -11.5 kcal/mol) for all lipid membranes examined. The relatively small variation of negative free energy of peptide binding together with a pronounced variation of positive enthalpy produces an equally strong variation of TDeltaS (+16.2 to +35.0 kcal/mol), indicating that GS14dK4 binding to phospholipids bilayers is primarily entropy driven.