Theoretical Calculation of the Liquid—Vapor Coexistence Curve of Water,Chloroform and Methanol with the Cavity-Biased Monte Carlo Method in the Gibbs Ensemble

Abstract

The Gibbs ensemble computer simulation method of Panagiotopoulos is combined by the cavity-biased sampling technique used previously in the grand-canonical ensemble. The combined technique is applied to the determination of the liquid—vapor coexistence curve of the Lennard—Jones fluid as a test case, two water models (SPC and TIP4P) as well as methanol and chloroform, both described with the OPLS model. The application of the virial-based sampling technique, used earlier in the isobaric ensemble is also discussed.     

Study of Liquid Dimethyl Sulfoxide by Computer Simulation

The paper reports Monte Carlo and molecular dynamicsresults for pure liquid dimethyl sulfoxide (DMSO) at298 K and 1 atm. The classical 6–12 Lennard–Jones plusCoulomb pairwise potential was used to calculateintermolecular interaction energy. Potentialparameters for the liquid were optimized in this work.Some thermodynamic and dynamical properties obtained,such as heat of vaporization, density and diffusioncoefficient, are in good agreement with theexperimental values. The present model is comparedwith other models for DMSO reported previously. It isshown to be an improvement over earlier potentials.The structure factors and the radial distributionfunctions (rdf), are compared with experimentalresults for the liquid. The analysis shows that thestructure of DMSO is not completely understood yet anddeserves deeper investigation. The geometry of thedimer that corresponds to the rdf plots obtained, isreported. The results suggest that the dipole momentof this dimer plays an important role in the structureof the liquid.     

Density functional theory characterisation of 4-hydroxyazobenzene

We report the structural properties, infrared (IR) and Raman spectra, dipole moment, polarisability, hardness and chemical potential of the trans and cis configurations of 4-hydroxyazobenzene calculated using the B3LYP functionals. All calculations were performed with the following basis sets: 6–31G, 6–31++G, 6–31G(d,p), 6–31++G(d,p), 6–31G(2d,2p), 6–31++G(2d,2p) and 6–311++G(2d,2p). We observed that 6–31++G(d,p) gives similar results to 6–311++G(2d,2p). Consequently, SVWN and PW91 methods were also used in association with 6–31++G(d,p) to test the influence of the different models of exchange and correlation functionals. A planar structure was obtained for all the optimised trans configuration structures. In both isomers, the presence of the hydroxyl group leads to an asymmetry in certain structural parameters. From these results, two IR or Raman active frequencies can be used to easily distinguish trans and cis configurations. The trans configuration was found to be more stable than the cis configuration by 67 ± 2 kJ mol⁻¹ at 0 K. The difference of the dipole moment between trans and cis for 4-hydroxyazobenzene was found to be lower than for trans and cis azobenzene.     

Influence of sample pH on the conformational backbone dynamics of a pseudotripeptide (H-Tyr-TicΨ[CH2-NH] Phe-OH) incorporating a reduced peptide bond: An NMR investigation

In the present paper we investigate the influence of sample pH on the conformational and dynamical properties of the pseudotripeptide H-Tyr-TicΨ[CH₂NH]Phe-OH(TIP[Ψ]:Tic: l, 2, 3, 4,-tetrahydroisoquinoline-3-carboxylic acid) using various one- and two-dimensional nmt techniques in conjunction with molecular modeling. Studies were conducted at three different pH levels-corresponding to the zwitterionic peptide containing a formal positive charge(pH 3. 1).the deprotonated molecule(pH 9. 1), and a situation at neutral pH(pH 7. 2) involving both protonated and deprotonated states of the reduced peptide bond. Analysis of the one-dimensional¹H-nmr spectra reveals that in solution TIP[Ψ]is in slow dynamic exchange between conformations containing cis and trans configurations of the Tyr-Tic bond. An nmr pH dependence study of the cis:trans ratio indicated that the exchange process was governed by the protonation state of the reduced bond amine. From the nmr data, reduced peptide bond pK_avalues of 6. 5 and 7. 5 were determined for the cis and trans conformers, respectively. It was concluded that conformations containing a trans Tyr-Tic bond are stabilized at law pH by an intramolecular hydrogen bond between the Tyr carbonyl and the reduced peptide bond protonated amine. This observation was corroborated by molecular mechanics investigations that revealed low energy trans structures compatible with nmr structural data, and furthermore, were consistently characterized by the existence of a strong N⁺ H?O? C interaction closing a seven-membered cycle. The dynamics of cis-trans isomerization about the Tyr-Tic peptide bond were probed by nmr exchange experiments. The selective presaturation of exchanging resonances carried out at several temperatures between 50 and 70°C allowed the determination of isomerization rate constants as well as thermodynamic activation parameters. ΔG^≠ values were in close agreement with the cis → trans energy barrier found in X-Pro peptide fragments (～83 kJ/mol).A large entropic barrier determined for the trans → cis conversion of TIP[Ψ](5. 7 JK^?1 mol^?1 at pH 3. 1; 6. 5 JK^?1 mol^?1 at pH 9. 1) is discussed in terms of decreased solvent molecular ordering around the conformers possessing a trans Tyr-Tic bond. Evidence that the neutral form of the reduced peptide bond gains rigidity upon protonation was obtained from relaxation measurements in the rotating frame. T_Jp measurements of several protons in the vicinity of the reduced peptide bond were made as a function of spin-lock field. Quantitative analysis of the relaxation data indicated that chemical shift fluctuations in the 10^?4-10^?5s range were more pronounced in the case of deprotonated TIP[Ψ]. Results of molecular dynamics simulations in addition to ³ J _αβ coupling constant measurements support the experimentally observed greater flexibility in the C-terminal region of TIP[Ψ]. © 1995 John Wiley & Sons, Inc.     

Effect of steric molecular field settings on CoMFA predictivity

Steric molecular field can be represented in a number of ways in comparative molecular field analysis (CoMFA). This study aimed to investigate whether the choice of steric molecular field settings significantly influences the predictive performance of CoMFA and, if so, which is the best. The three-dimensional quantitative structure activity relationship (3D-QSAR) models based on Lennard–Jones, indicator, parabolic and Gaussian steric fields were compared using 28 datasets taken from the literature. The analysis of the predictive ability of these models (cross validated R²) indicates that steric fields in which the value drops off quickly with distance (i.e. Lennard–Jones and indicator fields) tend to perform better than the Gaussian version, which has a slower and smoother decrease. Furthermore, depending on the steric field type used, the field sampling density (i.e. grid spacing) has a variable influence on the predictive ability of the models generated. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

FKBP-like catalysis of peptidyl-prolyl bond isomerization by micelles and membranes

Under physiological conditions, peptidyl-prolyl cis/trans isomerases catalyze powerfully the cis/trans isomerization of the -Xaa-Pro- bond (Xaa: natural amino acids) in oligopeptides and proteins (PPIases; EC 5.2.1.8). However, incorporation of proline containing tetrapeptide-4-nitroanilides in micelles and phospholipid vesicles also leads to increased rates of this unimolecular conformational interconversion. The isomerization rate was dependent on the detergent and vesicle concentration, respectively. The observed rate constants fit the pseudophase model of micellar catalysis allowing the calculation of micellar turnover numbers (k_cis^mic) and dissociation constants (K_C^mic). Comparing k_cis^mic values to the rate constants of the uncatalyzed cis to trans isomerization, an acceleration factor of about 20-fold was obtained for Suc-Ala-Phe-Pro-Phe-4-nitroanilide (Suc: succinyl) bound to zwitterionic SB12 (N-dodecyl-N,N-dimethylammonium-3-propanesulfonate) micelles. In addition, a marked increase in the population of the trans conformer relative to cis was noted for all investigated combinations of peptides and detergents. In a series of tetrapeptides, Suc-Ala-Xaa-Pro-Phe-4-nitroanilide k_cis^mic/K_C^mic as well as k_cis^mic values are linearly correlated with the high performance liquid chromatography capacity factor R′ describing the hydrophobicity of the amino acid Xaa. The same correlation can describe quantitatively the dependency of k_car/K_m on substrate hydrophobicity for the FKBP12-catalyzed isomerization. Despite the great differences in catalytic power, these results confirm the suspicion that micelles and FKBP12 may share a common component in the catalytic mechanism of peptidyl-prolyl bond isomerization. © 1997 John Wiley & Sons, Inc. Biopoly 42: 49–60, 1997     

Enhanced stability of cis Pro-Pro peptide bond in Pro-Pro-Phe sequence motif

Identification of sequence motifs that favor cis peptide bonds in proteins is important for understanding and designing proteins containing turns mediated by cis peptide conformations. From (1)H NMR solution studies on short peptides, we show that the Pro-Pro peptide bond in Pro-Pro-Phe almost equally populates the cis and trans isomers, with the cis isomer stabilized by a CHc...pi interaction involving the terminal Pro and Phe. We also show that Phe is over-represented at sequence positions immediately following cis Pro-Pro motifs in known protein structures. Our results demonstrate that the Pro-Pro cis conformer in Pro-Pro-Phe sequence motifs is as important as the trans conformer, both in short peptides as well as in natively folded proteins.     

Cis-trans isomerization of an angiotensin I-converting enzyme inhibitor. An enzyme kinetic and nuclear magnetic resonance study

The angiotensin I-converting enzyme (peptidyl-dipeptide hydrolase, EC 3.4.15.1) inhibitor, ramiprilat (2-[N-[(S)-1-ethoxycarbonyl-3-phenylpropyl]-L-Ala]-(1S,3S,5S)-2- azabicyclo[3.3.0]octane-3-carboxylic acid), is shown to exist in tow conformational isomers, cis and trans, which interconvert around the amide bond. The two conformers were separated by reversed-phase high-performance liquid chromatography. The conformers were identified by nuclear Overhauser effect measurements. From line shape analysis the isomerization rate constants were determined to be kcis----trans = 15 s-1 and ktrans----cis = 5 s-1 at 368 K in [2H]phosphate buffer (p2H 7.5). By enzyme kinetic studies using 3-(2-furylacryloyl)-L-Phe-Gly-Gly as substrate, the trans conformer was found to be the most potent enzyme inhibitor, whereas the cis conformer had a very low inhibitory effect. A new inhibition mechanism is presented for this type of slow, tight-binding inhibitors that contain an amide bond. This mechanism involves an equilibrium between the two conformers and the enzyme-bound inhibitor complex.     

Chemical Scale Studies of the Phe-Pro Conserved Motif in the Cys Loop of Cys Loop Receptors

The functions of two conserved residues, Phe¹³⁵ and Pro¹³⁶, located at the apex of the Cys loop of the nicotinic acetylcholine receptor are investigated. Both residues were substituted with natural and unnatural amino acids, focusing on the role of aromaticity at Phe¹³⁵, backbone conformation at Pro¹³⁶, side chain polarity and volume, and the specific interaction between the aromatic side chain and the proline. NMR spectroscopy studies of model peptides containing proline and unnatural proline analogues following a Phe show a consistent increase in the population of the cis conformer relative to peptides lacking the Phe. In the receptor, a strong interaction between the Phe and Pro residues is evident, as is a strong preference for aromaticity and hydrophobicity at the Phe site. A similar influence of hydrophobicity is observed at the proline site. In addition, across a simple homologous series of proline analogues, the results reveal a correlation between receptor function and cis bias at the proline backbone. This could suggest a significant role for the cis proline conformer at this site in receptor function.     

Potential metabolites of dimethoate produced by bacterial degradation

Microbial degradation of pesticide has been recognized as a potential solution for the disposal of pesticide. Two bacterial strains namely Bacillus licheniformis and Pseudomonas aeruginosa, which were isolated from water and fish intestine, respectively, were allowed to grow in mineral salt solution. The acetonitrile extracts of the bacterial cultures were subjected to thin layer chromatography using two different solvent systems: hexane–chloroform–methanol and cyclohexane–acetone–chloroform. The chromatogram revealed the presence of four metabolites of dimethoate with different R_f values, in the original P. aeruginosa strain using both hexane–chloroform–methanol and cyclohexane–acetone–chloroform solvent systems. Total disappearance of dimethoate spot occurred in the culture of B. licheniformis strain at day 3. Thus, the present study establishes the bacterial degradation of dimethoate and also suggests the role of bacteria in the bioremediation of pesticides.     

Salt effects on peptide conformers: a dielectric study of tuftsin.

Four 1-ns molecular dynamics computer simulations of tuftsin, Thr-Lys-Pro-Arg, are analyzed: (1) cis tuftsin in water, (2) trans tuftsin in water, (3) cis tuftsin in 1 M NaCl, and (4) trans tuftsin in 1 M NaCl. Independently of the salt concentration, the trans conformer has a higher dielectric constant than the cis conformer because the former exhibits a more widely distributed charge distribution in space. Independently of the peptide conformation, the presence of salt reduces the dielectric constants of both the peptide and the solvating water molecules because ions, on binding, restrict the motion of other atoms. In contrast to the dielectric constants, neither the peptide conformation nor the salt concentration shows a significant influence on the dielectric relaxation time of water molecules.     

The mineralization of chloroform in river sediments

The formation of¹⁴CO₂ from 3 μg l⁻¹ labelled chloroform was studied in anaerobic Dutch river sediments. All incubations were performed under anaerobic conditions. The observed first order mineralization kinetics showed half-lives of 2–37 days at 20°C in 12 muddy sediments. In contrast most of the sandy sediment samples did not show a mineralization of chloroform. Most probable number analysis revealed about 3.10⁴ chloroform mineralizing bacteria per g of dry sediment in a muddy sediment and 1–2.10³ chloroform mineralizing bacteria per g of dry sediment in a sandy sediment. Therefore the persistence of chloroform in sandy sediments is not caused by the absence of chloroform mineralizing bacteria but by the inactivity of these bacteria. This inactivity of the sandy sediments might allow chloroform from infiltrating river water to reach the groundwater. Mud samples from a relatively unpolluted site showed a similar chloroform mineralization rate compared with the polluted sediments from the rivers Rhine and Meuse. The data indicate that the reductive dechlorination of aliphatic compounds is not influenced at the polluted sites.     

Conformations of cyclo(L-orD-Phe-L-Pro-Aca) and cyclo(L-Pro-L- or D-Phe-Aca). Cyclized dipeptide models for specific types of beta-bends

Conformational analyses on four cyclic model peptides of the beta-bend, cyclo(L- or D-Phe-L-Pro-epsilon-aminocaproyl(Aca] and cyclo(L-Pro-L- or D-Phe-Aca), were carried out both experimentally and theoretically. Cyclo(D-Phe-L-Pro-Aca) was shown to exist as a single conformer taking the type II' beta-bend. The comparison of its CD spectra with those of cyclo(L-Ala-L-Ala-Aca) revealed that type I and II' beta-bends, both with alpha-helix-like CD spectra, can be distinguished. Cyclo(L-Phe-L-Pro-Aca) was shown to exist as a single conformer with a cis L-Phe-L-Pro peptide bond, taking the type VI beta-bend. Its CD spectrum has thus been observed for the first time for the bend containing a cis peptide bond. Cyclo(L-Pro-L-Phe-Aca) was shown to exist as a mixture of two conformers, the major one taking the type I beta-bend with a trans Aca-L-Pro peptide bond and the minor one with a cis Aca-L-Pro peptide bond. Cyclo(L-Pro-D-Phe-Aca) was suggested to exist as a mixture of two conformers, the major one taking the type II beta-bend with a trans Aca-L-Pro peptide bond and the minor one with a cis Aca-L-Pro peptide bond.     

Proline-containing beta-turns. IV. Crystal and solution conformations of tert.-butyloxycarbonyl-L-prolyl-D-alanine and tert.-butyloxycarbonyl-L-prolyl-D-alanyl-L-alanine

The conformations of the dipeptide t-Boc-Pro-DAla-OH and the tripeptide t-Boc-Pro-DAla-Ala-OH have been determined in the crystalline state by X-ray diffraction and in solution by CD, n.m.r. and i.r. techniques. The unit cell of the dipeptide crystal contains two independent molecules connected by intermolecular hydrogen bonds. The urethane-proline peptide bond is in the cis orientation in both the molecular forms while the peptide bond between Pro and DAla is in the trans orientation. The single dipeptide molecule exhibits a "bent" structure which approximates to a partial beta-turn. The tripeptide adopts the 4----1 hydrogen-bonded type II beta-turn with all trans peptide bonds. In solution, the CD and i.r. data on the dipeptide indicate an ordered conformation with an intramolecular hydrogen bond. N.m.r. data indicate a significant proportion of the conformer with a trans orientation at the urethane-proline peptide bond. The temperature coefficient of the amide proton of this conformer in DMSO-d6 points to a 3----1 intramolecular hydrogen bond. Taken together, the data on the dipeptide in solution indicate the presence (in addition to the cis conformer) of a C7 conformation which is absent in the crystalline state. The spectral data on the tripeptide indicate the presence of the type II beta-turn in solution in addition to the nonhydrogen-bonded conformer with the cis peptide bond between the urethane and proline residues. The relevance of these data to studies on the substrate specificity of collagen prolylhydroxylase is pointed out.     

Two conformational states of Turkey ovomucoid third domain at low pH: three-dimensional structures,internal dynamics,and interconversion kinetics and thermodynamics

Turkey ovomucoid third domain (OMTKY3) is shown to exist at low pH as two distinctly folded, interconverting conformations. Activation parameters were determined for the transition, and these were of the type reported previously for cis/trans isomerizations of prolyl peptide bonds. Multidimensional, multinuclear NMR spectroscopy was used to determine the three-dimensional structure of each of the two states of P(5)-Pro(14)Asp OMTKY3 at pH 2.5 and 25 degrees C, under conditions where the two states have equal populations with interchange rates of 0.25 s(-1). The results showed that the two states differ by cis/trans isomerization of the P(8)-Tyr(11)-P(7)-Pro(12) peptide bond, which is cis in the conformer dominant at neutral pH and trans in the conformer appearing at low pH. The major structural differences were found to be in the region of the reactive site loop. The core of the protein, including the antiparallel beta-sheet and a alpha-helix, is preserved in both structures. The state with the cis peptide bond is similar to previously reported structures of OMTKY3 determined by NMR spectroscopy and X-ray crystallography. The cis-to-trans transition results in the relocation of the aromatic ring of P(8)-Tyr(11), disrupts many interactions between the alpha-helix and the reactive-site loop, and leads to more open spacing between this loop and the alpha-helix. In addition, the configurations of two of the three disulfide bonds, P(11)-Cys(8)- P(20)'-Cys(38), and P(3)-Cys(16)- P(17)'-Cys(35), are altered such that the C(alpha)-C(alpha) distances for each disulfide bridge are longer by approximately 1 A in the trans state than in the cis. Mutations at P(1)-Leu(18), P(6)-Lys(13), and P(5)-Pro(14) influence the position of the cis <= => trans equilibrium. In P(1)-Leu(18)Xxx OMTKY3 mutants, the trans state is more favored by P(1)-Gly(18) than by Ala(18) or Leu(18); in P(6)-Lys(13)Xxx OMTKY3 mutants, the trans state is more favored by P(6)-Glu(13) and P(6)-Asp(13) than Lys(13) or His(13). Stabilization of the trans state in P(5)-Pro(14)Xxx OMTKY3 mutants follows the series Xxx = Gly > Asp > Glu > Ala approximately equal His > Pro. In comparing the state with the trans peptide bond to that with the cis, the pK(a) values of P(12)-Asp(7) and P(1)'-Glu(19) are higher and those of P(9)-Glu(10) and P(25)'-Glu(43) are lower. The pK(a) values of other titrating groups in the molecule are similar in both conformational states. These pK(a) changes underlie the pH dependence of the conformational equilibrium and can be explained in part by observed structural differences. (15)N transverse relaxation results indicate that residues P(6)-Lys(13)-P(3)-Cys(16) in the trans state undergo a dynamic process on the microsecond-millisecond time scale not present in the cis state.     

Biodegradation of commercial linear alkyl benzenes byNocardia amarae

Laboratory degradation studies of two indigeneously produced linear alkyl benzenes byNocardia amarae MB-11 isolated from soil showed an overall degradation of linear alkyl benzenes isomers to the extent of 57–70%. Degradation of 2-phenyl isomers of linear alkyl benzenes was complete and faster than that of other phenyl position (C3–C7) isomers which were degraded to the extent of 40–72% only. Length of alkyl side chains (C₁₀–C₁₄) had little or no impact on the degradation pattern. Major metabolities detected were 2-, 3-and 4-phenyl butyric acids, phenyl acetic acid and cis, cis-muconic acid. Minor metabolites weretrans-cinnamic acid, 4-phenyl 3-butenoic acid and 3-phenyl pentanoic acid along with two unidentified hydroxy acids. On the basis of the formation pattern of these metabolities, three catabolic pathways of linear alkyl benzenes isomers inNocardia amarae MB-11 were postulated. All the phenyl position (C2–C7) isomers of C₁₀, C₁₂, and C₁₄ linear alkyl benzenes along with 3-phenyl and 5-phenyl isomers of C₁₁ and C₁₃ linear alkyl benzenes were degraded viacis,cis-muconic acid pathway. Other phenyl position isomers of C₁₁ and C₁₃ linear alkyl benzenes with phenyl substitution at even number carbon atoms were principally degraded via phenyl acetic acid pathway whiletrans-cinnamic acid formation provided a minor pathway     

The comparative in vitro pharmacology of leukotriene D4 and its isomers

The 5R,6S and 5S,6R isomers of leukotriene D₄ (LTD₄), 9cis LTD₄, 9cis,11trans LTD₄ and 11trans LTD₄ were synthesized for comparative pharmacological studies on intestinal and respiratory smooth muscle preparations. The 5S,6R isomers are biologically active, modification of the double bond stereochemistry causing only a moderate reduction in activity. The 5R,6S isomers possess approximately 1% the biological activity of their respective 5S,6R forms.     

Solvent-mediated conformational transition in β-alanine containing cyclic peptides. VIII

In the present paper we describe the solution nmr structural analysis and restrained molecular dynamic simulation of the cyclic pentapeptide cyclo-(Pro-Phe-Phe-β-Ala-β-Ala). The conformational analysis carried out in CD₃CN and dimethylsulfoxide (DMSO) solutions by nmr spectroscopy was based on interproton distances derived from rotating frame nuclear Overhauser effect spectroscopy spectra and homonuclear coupling constants. A restrained molecular dynamic simulation in vacuo was also performed to build refined molecular models. The molecule is present in both solvent systems as two slowly interconverting conformers, characterized by a cis-trans isomerism around the β-Ala⁵-Pro¹ peptide bond. In CD₃CN solution, the conformer with a cis peptide bond is quite similar to that observed in the solid state, while the conformer containing all trans peptide bonds is characterized by an intramolecular hydrogen bond stabilizing a C₁₀- and a C₁₃-ring structure. In DMSO solution, the trans isomer is partly similar to that observed in CD₃CN solution while the cis isomer is different from that observed in the solid state. The effect of the solvent in stabilizing different conformations was also investigated in DMSO-CD₃CN solvent mixtures. © 1996 John Wiley & Sons, Inc.