Peptides In Aqueous Solution Research Articles

Effect of Solvent Choice on the Self-Assembly Properties of a Diphenylalanine Amphiphile Stabilized by an Ion Pair.

A diphenylalanine (FF) amphiphile blocked at the C terminus with a benzyl ester (OBzl) and stabilized at the N terminus with a trifluoroacetate (TFA) anion was synthetized and characterized. Aggregation of peptide molecules was studied by considering a peptide solution in an organic solvent and adding pure water, a KCl solution, or another organic solvent as co-solvent. The choice of the organic solvent and co-solvent and the solvent/co-solvent ratio allowed the mixture to be tuned by modulating the polarity, the ionic strength, and the peptide concentration. Differences in the properties of the media used to dissolve the peptides resulted in the formation of different self-assembled microstructures (e.g. fibers, branched-like structures, plates, and spherulites). Furthermore, crystals of TFA⋅FF-OBzl were obtained from the aqueous peptide solutions for X-ray diffraction analysis. The results revealed a hydrophilic core constituted by carboxylate (from TFA), ester, and amide groups, and the core was found to be surrounded by a hydrophobic crown with ten aromatic rings. This segregated organization explains the assemblies observed in the different solvent mixtures as a function of the environmental polarity, ionic strength, and peptide concentration.

Effects of different force fields on the structural character of α synuclein β-hairpin peptide (35–56) in aqueous environment

The hallmark of Parkinson’s disease (PD) is the intracellular protein aggregation forming Lewy Bodies (LB) and Lewy neuritis which comprise mostly of a protein, alpha synuclein (α-syn). Molecular dynamics (MD) simulation methods can augment experimental techniques to understand misfolding and aggregation pathways with atomistic resolution. The quality of MD simulations for proteins and peptides depends greatly on the accuracy of empirical force fields. The aim of this work is to investigate the effects of different force fields on the structural character of β hairpin fragment of α-syn (residues 35–56) peptide in aqueous solution. Six independent MD simulations are done in explicit solvent using, AMBER03, AMBER99SB, GROMOS96 43A1, GROMOS96 53A6, OPLS-AA, and CHARMM27 force fields with CMAP corrections. The performance of each force field is assessed from several structural parameters such as root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), solvent accessible surface area (SASA), formation of β-turn, the stability of folded β-hairpin structure, and the favourable conformations obtained for different force fields. In this study, CMAP correction of CHARMM27 force field is found to overestimate the helical conformation, while GROMOS96 53A6 is found to most successfully capture the conformational dynamics of α-syn β-hairpin fragment as elicited from NMR.

Nonequilibrium Self-Assembly of π-Conjugated Oligopeptides in Solution.

Supramolecular assembly is a powerful method that can be used to generate materials with well-defined structures across multiple length scales. Supramolecular assemblies consisting of biopolymer-synthetic polymer subunits are specifically known to exhibit exceptional structural and functional diversity as well as programmable control of noncovalent interactions through hydrogen bonding in biopolymer subunits. Despite recent progress, there is a need to control and quantitatively understand assembly under nonequilibrium conditions. In this work, we study the nonequilibrium self-assembly of π-conjugated synthetic oligopeptides using a combination of experiments and analytical modeling. By isolating an aqueous peptide solution droplet within an immiscible organic layer, the rate of peptide assembly in the aqueous solution can be controlled by tuning the transport rate of acid that is used to trigger assembly. Using this approach, peptides are guided to assemble under reaction-dominated and diffusion-dominated conditions, with results showing a transition from a diffusion-limited reaction front to spatially homogeneous assembly as the transport rate of acid decreases. Interestingly, our results show that the morphology of self-assembled peptide fibers is controlled by the assembly kinetics such that increasingly homogeneous structures of self-assembled synthetic oligopeptides were generally obtained using slower rates of assembly. We further developed an analytical reaction-diffusion model to describe oligopeptide assembly, and experimental results are compared to the reaction-diffusion model across a range of parameters. Overall, this work highlights the importance of molecular self-assembly under nonequilibrium conditions, specifically showing that oligopeptide assembly is governed by a delicate balance between reaction kinetics and transport processes.

Thermodynamic characteristics of protolytic equilibria in aqueous solutions of glycyl peptides

Protolytic equilibria in aqueous solutions of glycyl-DL-serine, glycyl-DL-threonine, and glycyl-DL-valine are investigated by means of potentiometry and calorimetry. Dissociation constants and heat effects of the above dipeptides are determined. Standard thermodynamic characteristics (pK°, ΔdisG°, ΔdisH°, ΔdisS°) of the investigated equilibria are calculated. The obtained results are compared to corresponding data on relative compounds.

PEP-FOLD3: faster de novo structure prediction for linear peptides in solution and in complex.

Structure determination of linear peptides of 5–50 amino acids in aqueous solution and interacting with proteins is a key aspect in structural biology. PEP-FOLD3 is a novel computational framework, that allows both (i) de novo free or biased prediction for linear peptides between 5 and 50 amino acids, and (ii) the generation of native-like conformations of peptides interacting with a protein when the interaction site is known in advance. PEP-FOLD3 is fast, and usually returns solutions in a few minutes. Testing PEP-FOLD3 on 56 peptides in aqueous solution led to experimental-like conformations for 80% of the targets. Using a benchmark of 61 peptide–protein targets starting from the unbound form of the protein receptor, PEP-FOLD3 was able to generate peptide poses deviating on average by 3.3Å from the experimental conformation and return a native-like pose in the first 10 clusters for 52% of the targets. PEP-FOLD3 is available at http://bioserv.rpbs.univ-paris-diderot.fr/services/PEP-FOLD3.

A polarizable QM/MM approach to the molecular dynamics of amide groups solvated in water.

The infrared (IR) spectra of polypeptides are dominated by the so-called amide bands. Because they originate from the strongly polar and polarizable amide groups (AGs) making up the backbone, their spectral positions sensitively depend on the local electric fields. Aiming at accurate computations of these IR spectra by molecular dynamics (MD) simulations, which derive atomic forces from a hybrid quantum and molecular mechanics (QM/MM) Hamiltonian, here we consider the effects of solvation in bulk liquid water on the amide bands of the AG model compound N-methyl-acetamide (NMA). As QM approach to NMA we choose grid-based density functional theory (DFT). For the surrounding MM water, we develop, largely based on computations, a polarizable molecular mechanics (PMM) model potential called GP6P, which features six Gaussian electrostatic sources (one induced dipole, five static partial charge distributions) and, therefore, avoids spurious distortions of the DFT electron density in hybrid DFT/PMM simulations. Bulk liquid GP6P is shown to have favorable properties at the thermodynamic conditions of the parameterization and beyond. Lennard-Jones (LJ) parameters of the DFT fragment NMA are optimized by comparing radial distribution functions in the surrounding GP6P liquid with reference data obtained from a "first-principles" DFT-MD simulation. Finally, IR spectra of NMA in GP6P water are calculated from extended DFT/PMM-MD trajectories, in which the NMA is treated by three different DFT functionals (BP, BLYP, B3LYP). Method-specific frequency scaling factors are derived from DFT-MD simulations of isolated NMA. The DFT/PMM-MD simulations with GP6P and with the optimized LJ parameters then excellently predict the effects of aqueous solvation and deuteration observed in the IR spectra of NMA. As a result, the methods required to accurately compute such spectra by DFT/PMM-MD also for larger peptides in aqueous solution are now at hand.

Lepidopteran defence droplets - a composite physical and chemical weapon against potential predators.

Insects often release noxious substances for their defence. Larvae of Zygaena filipendulae (Lepidoptera) secrete viscous and cyanogenic glucoside-containing droplets, whose effectiveness was associated with their physical and chemical properties. The droplets glued mandibles and legs of potential predators together and immobilised them. Droplets were characterised by a matrix of an aqueous solution of glycine-rich peptides (H-WG11-NH2) with significant amounts of proteins and glucose. Among the proteins, defensive proteins such as protease inhibitors, proteases and oxidases were abundant. The neurotoxin β-cyanoalanine was also found in the droplets. Despite the presence of cyanogenic glucosides, which release toxic hydrogen cyanide after hydrolysis by a specific β-glucosidase, the only β-glucosidase identified in the droplets (ZfBGD1) was inactive against cyanogenic glucosides. Accordingly, droplets did not release hydrogen cyanide, unless they were mixed with specific β-glucosidases present in the Zygaena haemolymph. Droplets secreted onto the cuticle hardened and formed sharp crystalline-like precipitates that may act as mandible abrasives to chewing predators. Hardening followed water evaporation and formation of antiparallel β-sheets of the peptide oligomers. Consequently, after mild irritation, Zygaena larvae deter predators by viscous and hardening droplets that contain defence proteins and β-cyanoalanine. After severe injury, droplets may mix with exuding haemolymph to release hydrogen cyanide.

The interplay of aggregation, fibrillization and gelation of an unexpected low molecular weight gelator: glycylalanylglycine in ethanol/water.

Hydrogels formed by polypeptides could be much-favored tools for drug delivery because their main ingredients are generally biodegradable. However, the gelation of peptides in aqueous solution generally requires a minimal length of the peptide as well as distinct sequences of hydrophilic and hydrophobic residues. The aggregation of short peptides like tripeptides, which are relatively cheap and offer a high degree of biodegradability, are generally thought to require a high hydrophobicity of their residues. We found that contrary to this expectation cationic glycylalanylglycine in 55 mol% ethanol/45 mol% water forms a gel below a melting temperature of ca. 36 °C. A pure hydrogel state can be obtained after allowing the ethanol component to evaporate. The gel phase consists of crystalline fibrils of several 100 μm, which form a sample-spanning network. Rheological data reveal a soft elastic solid gel. We investigated the kinetics of the various processes that lead to the final gel state of the ternary mixture by a unique combination of UV circular dichroism, infrared, vibrational circular dichroism (VCD) and rheological measurements. A mathematical analysis of our data show that gelation is preceded by the formation of peptide β-sheet like tapes or ribbons, which give rise to a significant enhancement of the amide I' VCD signal, and the subsequent formation of rather thick and long fibrils. The VCD signals indicate that the tapes exhibit a right-handed helicity at temperatures above 16 °C and a left-handed helicity below. The tapes'/ribbons' helicity change occurs at a temperature where the UVCD data reflect a relatively long nucleation process. The kinetics of gel formation probed by the storage and loss moduli are composed of a fast process that follows tape/ribbon/fibril formation and is clearly identifiable in a movie that shows the gelation process and a slow process that causes an additional gel stabilization. The rheological data indicate that left-handed fibrils observed at low temperatures form a more solid-like structure than their right-handed counterparts formed at higher temperatures. Taken together our data reveal GAG as an unexpected gelator, the formation of which is underlied by a set of distinguishable kinetic processes.

Development and characterization of functionalized self-assembling nanopeptide on the effect of angiogenesis for injured brain tissue regeneration

Event Abstract Back to Event Development and characterization of functionalized self-assembling nanopeptide on the effect of angiogenesis for injured brain tissue regeneration Kai-Chiech Chang1, Yung-Jen Chuang2, Wen-Han Chang3, Ming-Yuan Huang3 and Tzu-Wei Wang1 1 National Tsing Hua University, Department of Materials Science and Engineering, Taiwan 2 National Tsing Hua University, Department of Medical Science & Institute of Bioinformatics and Structural Biology, Taiwan 3 Mackay Memorial Hospital, Department of Emergency, Taiwan Introduction: Tissue and organ regeneration has been regarded as an optimal therapeutic strategy for traumatic brain injury. In this study, we proposed a three-dimensional (3D) hydrogel matrix to facilitate neoangiogenesis around damaged brain wound region[1]-[3]. A functionalized peptide, RADA16-SVVYGLR (AcN-RADARADARADARADASVVYGLR-CONH2), is designed, synthesized, and self-assembles into nanofibers network to form hydrogel with fiber entanglements[4]. The hydrogel with mechanical stiffness provides a suitable substrate for encapsulated neural stem cells adhesion and differentiation. The functional peptide, SVVYGLR, had been shown to regulate growth of hemopoietic stem cells and to induce angiogenesis[5],[6]. From previous in vitro and in vivo study, the hydrogel made of RADA16-SVVYGLR was compatible for cells proliferation in zebrafish embryos development. We expect that functionalized peptide hydrogel would create a favorable microenvironment for neural tissue repair and serve as a potential therapeutic application in traumatic brain damages. Method: Peptide solution: All aqueous peptide solutions were prepared by dissolving in Milli-Q water, stored at 4°C. Physiochemical properties analyses: Peptide secondary structure, nanofibers morphology and hydrogel rheology were analyzed by circular dichroism (CD), transmission electron microscopy (TEM), and rheometer, respectively. In vivo study: Zebrafish line (Tg(kdr:EGFP)) were used to perform zebrafish embryo toxicity test (zFET) including analysis of the survival rate and the development of intersegmental vessels (ISVs). Results and Discussion: The CD spectrum showed RADA16 and RADA16-SVVYGLR were in the form of beta sheet with minimum at 216 nm and maximum at 196 nm (Fig. 1). Morphology of both peptides were nanofibers network, developing scaffolds favorable to cellular processes and molecules transportation (Fig. 2). As the CD and TEM results, the self-assembling mechanism was not changed dramatically after linking the motif on the terminal of RADA16. The rheology of hydrogels showed that G’ was higher than G’’, indicating the gel-like property. (Fig. 3) The survival rate of fish embryos treated with peptide hydrogel was similar to that in the control group (Fig. 4). After 72 hours post-fertilization, the phenotypic traits of ISVs growth were identical in fish treated with hydrogel and that in control group, showing the normal physiological growth of ISVs to the DLAVs and PCVs. (Fig. 5) The zFET showed toxicity was not observed. Conclusion: The self-assembling peptides in our study, characterized as beta sheet secondary structure with angiogenic sequence, formed into a gel-like 3D scaffold with nanofibers network which was a suitable matrix for NSCs proliferation and a biocompatible biomaterial by zebrafish animal model. The hydrogel scaffold by functionalized self-assembling peptide has a potential role in clinical application to improve tissue regeneration. Dr. Wen-Han Chang; Dr. Ming-Yuan Huang; Prof. Yung-Jen Chuang; NTHU-Mackay Memorial Hospital Joint Research Program (103N2770E1); Research funding support of Ministry of Science and Technology, R.O.C. (104-2628-E-007-002-MY3)

Direct exfoliation of graphite into graphene in aqueous solutions of amphiphilic peptides.

Different amphiphilic peptides were used to mediate the direct exfoliation of graphite into few-layered graphene flakes in aqueous solutions. Charge was found to be an important parameter in determining their graphite exfoliating efficiency. The anionic molecules were more favorable than the cationic ones leading to a higher efficiency. The gemini-type peptide IleIleIleCys-CysIleIleIle (I3C-CI3) exhibited the highest efficiency, which might be attributed to its specific physicochemical properties and interactions with graphene sheets. I3C-CI3 adsorbed onto the graphene surface as either monomers or self-assembled nanoaggregates. These adsorbed species increased both electrostatic and steric repulsions between the graphene/I3C-CI3 composites. More interestingly, the graphene/I3C-CI3 composites showed a reversible pH-dependent dispersion/aggregation. This behavior resulted from the pH-sensitive protonation of the peptide molecules and was rarely found in the graphene dispersions exfoliated by traditional surfactants. Moreover, the graphene/I3C-CI3 dispersion was used to fabricate free-standing macroscopic composite films that contained different nanostructures. The study expands the library of available agents for direct graphite exfoliation to produce graphene sheets. Employing peptide molecules as graphene exfoliating and stabilizing agents avoids the use of toxic reagents, which may allow fabrication of functional composite materials for biocompatible applications.

TIGER2 with solvent energy averaging (TIGER2A): An accelerated sampling method for large molecular systems with explicit representation of solvent.

The recently developed "temperature intervals with global exchange of replicas" (TIGER2) accelerated sampling method is found to have inaccuracies when applied to systems with explicit solvation. This inaccuracy is due to the energy fluctuations of the solvent, which cause the sampling method to be less sensitive to the energy fluctuations of the solute. In the present work, the problem of the TIGER2 method is addressed in detail and a modification to the sampling method is introduced to correct this problem. The modified method is called "TIGER2 with solvent energy averaging," or TIGER2A. This new method overcomes the sampling problem with the TIGER2 algorithm and is able to closely approximate Boltzmann-weighted sampling of molecular systems with explicit solvation. The difference in performance between the TIGER2 and TIGER2A methods is demonstrated by comparing them against analytical results for simple one-dimensional models, against replica exchange molecular dynamics (REMD) simulations for sampling the conformation of alanine dipeptide and the folding behavior of (AAQAA)3 peptide in aqueous solution, and by comparing their performance in sampling the behavior of hen egg-white lysozyme in aqueous solution. The new TIGER2A method solves the problem caused by solvent energy fluctuations in TIGER2 while maintaining the two important characteristics of TIGER2, i.e., (1) using multiple replicas sampled at different temperature levels to help systems efficiently escape from local potential energy minima and (2) enabling the number of replicas used for a simulation to be independent of the size of the molecular system, thus providing an accelerated sampling method that can be used to efficiently sample systems considered too large for the application of conventional temperature REMD.

Slow Internal Dynamics and Charge Expansion in the Disordered Protein CGRP: A Comparison with Amylin

We provide the first direct experimental comparison, to our knowledge, between the internal dynamics of calcitonin-gene-related peptide (CGRP) and amylin (islet amyloid polypeptide, IAPP), two intrinsically disordered proteins of the calcitonin peptide family. Our end-to-end contact formation measurements reveal that in aqueous solution (i.e., in the absence of structure-inducing organic solvents) CGRP preferentially populates conformations with short end-to-end distances. However, the end-to-end distance of CGRP is larger than that of IAPP. We find that electrostatic interactions can account for such a difference. At variance with previous reports on the secondary structure of CGRP, we find that the end-to-end distance of the peptide increases with decreasing pH and salt concentration, due to Coulomb repulsion by charged residues. Interestingly, our data show that the reconfiguration dynamics of CGRP is significantly slower than that of human IAPP in water but not in denaturant, providing experimental evidence for roughness in the energy landscape, or internal friction, in these peptides. The data reported here provide both structural and dynamical information that can be used to validate results from molecular simulations of calcitonin family peptides in aqueous solution.

Magnetic non-equivalence and dynamic NMR of N-methylene protons in a Histamine-containing pseudopeptide: Alanyl-Glycyl-Histamine

The objective of the present research is to explore the potential of an additional feature of proton 1D-NMR for the study of the properties of peptides in aqueous solution, namely the magnetic non-equivalence of N-methylene protons in linear acyclic peptides induced by an asymmetric carbon atom located nearby. For this exploratory study, we have chosen an l-Alanyl terminal residue adjacent to a Glycyl residue, itself grafted to an optically inactive terminal Histamine unit, i.e., the Histamine-containing pseudopeptide l-Alanyl-Glycyl-Histamine (AGHA). The pH- and temperature-dependence of magnetic non-equivalences of Glycyl and Histamine N-methylene protons was modeled as a weighted mean over four ionization states BH3, BH2, BH, B of AGHA molecules found in the pH range explored: pH −0.78 to 12. In parallel, this research has made it possible to assess the pK's governing the speciation curve, the base- and acid-catalyzed proton exchange rates and the pK's of amide bonds.

Randomizing the unfolded state of peptides (and proteins) by nearest neighbor interactions between unlike residues.

To explore the influence of nearest neighbors on conformational biases in unfolded peptides, we combined vibrational and 2D NMR spectroscopy to obtain the conformational distributions of selected "GxyG" host-guest peptides in aqueous solution: GDyG, GSyG, GxLG, GxVG, where x/y=A, K, L, V. Large changes of conformational propensities were observed due to nearest-neighbor interactions, at variance with the isolated pair hypothesis. We found that protonated aspartic acid and serine lose their above-the-average preference for turn-like structures in favor of polyproline II (pPII) populations in the presence of neighbors with bulky side chains. Such residues also decrease the above-the-average pPII preference of alanine. These observations suggest that the underlying mechanism involves a disruption of the hydration shell. Thermodynamic analysis of (3) J(H(N) ,H(α) ) (T) data for each x,y residue reveals that modest changes in the conformational ensemble masks larger changes of enthalpy and entropy governing the pPII↔β equilibrium indicating a significant residue dependent temperature dependence of the peptides' conformational ensembles. These results suggest that nearest-neighbor interactions between unlike residues act as conformational randomizers close to the enthalpy-entropy compensation temperature, eliminating intrinsic biases in favor of largely balanced pPII/β dominated ensembles at physiological temperatures.

Molecular Dynamics Simulations of 441 Two-Residue Peptides in Aqueous Solution: Conformational Preferences and Neighboring Residue Effects with the Amber ff99SB-ildn-NMR Force Field.

Understanding the intrinsic conformational preferences of amino acids and the extent to which they are modulated by neighboring residues is a key issue for developing predictive models of protein folding and stability. Here we present the results of 441 independent explicit-solvent MD simulations of all possible two-residue peptides that contain the 20 standard amino acids with histidine modeled in both its neutral and protonated states. (3)J(HNHα) coupling constants and δ(Hα) chemical shifts calculated from the MD simulations correlate quite well with recently published experimental measurements for a corresponding set of two-residue peptides. Neighboring residue effects (NREs) on the average (3)J(HNHα) and δ(Hα) values of adjacent residues are also reasonably well reproduced, with the large NREs exerted experimentally by aromatic residues, in particular, being accurately captured. NREs on the secondary structure preferences of adjacent amino acids have been computed and compared with corresponding effects observed in a coil library and the average β-turn preferences of all amino acid types have been determined. Finally, the intrinsic conformational preferences of histidine, and its NREs on the conformational preferences of adjacent residues, are both shown to be strongly affected by the protonation state of the imidazole ring.

Randomizing Intrinsic Conformational Biases by Nearest Neighbor Interactions between Unlike Residues

To explore the influence of nearest neighbors on conformational biases in unfolded model peptides, we combined vibrational (IR, Vibrational Circular Dichroism, Raman), and 2D-NMR spectroscopy to study selected “GxyG” host-guest peptides in aqueous solution: GDyG, GSyG, GxLG, GxVG, where x/y={A,K,LV}. To obtain the conformational ensemble of each x/y residue, we utilized an excitonic coupling theory based formalism to simulate experimental amide I’ profiles with conformational distributions composed of 2D-Gaussian distribution in Ramachandran space representing pPII-, β-strand-, helical-, and turn-like conformations. Experimental J coupling constants were similarly reproduced using these conformational distributions along with appropriate Karplus equations. Our data reveal large changes in conformational distributions due to neighbor interactions, contrary to the isolated pair hypothesis. Interestingly, residues that have large intrinsic biases towards specific sub-populations tend to loose these preferences upon interaction with a dissimilar neighbors, indicating a degree of conformational randomization. For instance, residues that prefer turn-like conformations (namely aspartic acid and serine) lose this turn preference in favor of increased pPII populations, which ultimately increases the total extended state sampling. In addition, we observe a decreased pPII content for alanine upon insertion of non-alanine neighbors, which generally increases with the bulkiness of the neighbors’ side chain. Strong effects induced by residues with bulky aliphatic side chains suggests that the underlying mechanism occurs through disruption of the hydration shell. Thermodynamic analysis of 3J(HNHα) (T) data for each x,y residue reveals that modest changes in the conformational ensemble masks larger changes of enthalpy and entropy governing the pPII/β equilibrium suggesting a significant residue dependent temperature dependence of the peptides’ conformational ensembles.

Free energy simulations of amylin I26P mutation in a lipid bilayer.

The amylin peptide in a dioleoylphosphatidylcholine (DOPC) bilayer is studied using united atom molecular dynamics (MD) simulations. Dynamics and transport properties of the peptide and the phospholipid bilayer are investigated. The lateral diffusion of DOPC is in the order of 10(-8) cm(2) s(-1), which is in agreement with the experimental results. The order parameter and density profile for phospholipid molecules in the bilayer are calculated. The secondary structure of amylin peptide shows that the amino acids in two terminals are structureless and two α-helical segments in the peptide are connected through an unstructured link. This structure is similar to the experimental structure in the membrane-mimicking media. Free energy calculations of the Ile26→Pro mutation in the amylin peptide are performed in the bilayer and in aqueous solution using molecular dynamics simulations and a thermodynamic cycle. It is shown that in the mutated peptide in aqueous solution, the α-helix structure changes to a 5-helix, whereas this configuration is preserved in the bilayer environment. It is interesting that the accessible surface area increases for hydrophobic residues in the bilayer and for hydrophilic residues in aqueous solution as the coupling parameter changes from 0 to 1. These results are significant to understanding the aggregation mechanism of human amylin monomers in membranes to the dimers, trimers, oligomers, and fibrils associated with the type 2 diabetes at the atomic level.

Capability of PHSC equation of state for thermodynamic modeling of aqueous amino acid and peptide solutions

The Perturbed Hard Sphere Chain (PHSC) equation of state (EoS) has been utilized for thermodynamic modeling of aqueous amino acid and peptide solutions. For this purpose, the parameters of amino acids and peptides have been adjusted to activity coefficient, liquid density and solubility of amino acids and peptides in water. Furthermore, water activity, osmotic coefficient and vapor pressure of aqueous amino acid solution have been predicted. Finally the solubility of amino acid mixtures in water has been calculated using additional adjustable parameters. The results of PHSC EoS were in good agreement with experimental data. Average deviations in estimation of activity coefficients, liquid densities, water activity and osmotic coefficient are 1.44%, 0.38%, 0.067% and 2.6%, respectively. In addition the solubility of mixed aqueous amino acids has been calculated to show the ability of mentioned model.

Solution structure of a designed cyclic peptide ligand for nickel and copper ions

Nuclear magnetic resonance (NMR) spectroscopy was used to study a cyclic peptide derived from the amino-terminal copper-and-nickel-binding (ATCUN) motif. The three-dimensional structure of the unliganded peptide in aqueous solution was solved by simulated annealing using distance constraints derived from Nuclear Overhauser Effects. A structural model for the Ni(II)-bound complex was also produced based on NMR evidence and prior spectroscopic data, which are consistent with crystal structures of linear ATCUN complexes. Structural interpolation, or ‘morphing’, was used to understand the transition of this highly structured cyclic peptide from its unliganded structure to its metal-ion-bound structure.

Enthalpy-Entropy Compensation and Isoequilbria Implicate Solvation as the Driving Force for Amino Acid Conformational Propensity

The existence of residual structure in intrinsically disordered proteins (IDPs) raise questions regarding how disorder/order preferences are encoded in the peptide sequence. In addition to formation of local secondary structure, individual amino acids sample unique and restricted conformational space, contrary to the predictions of the random coil model. To understand the thermodynamic driving forces underlying these newly discovered amino acid conformational biases, we have examined the thermodynamics governing these intrinsic conformational propensities in a series of host-guest experiments on model “GxG” peptides in aqueous solution. Global two-state pPII/β thermodynamic analysis of UVCD and HNMR data revealed the existence of a nearly exact enthalpy-entropy compensation for the pPII-β equilibrium for all residues. The obtained ΔH/ΔS values exhibit a nearly perfect linear relationship reflecting compensation temperature of 295K ± 2 K. We identified iso-equilibria for two subsets of the investigated peptides, indicating that pPII and β propensities of most residues become similar at physiological temperature, in spite of rather large differences between respective enthalpic and entropic differences. Interestingly, alanine, aspartic acid, and threonine, which have largely biased intrinsic conformational propensities, are the only amino acid residues that do not share iso-equilibria. We assign the isoequilibria to a common enthalpy-entropy compensation which occurs in the hydration shell of side chains with considerable hydrophobic content. Aspartic acid and threonine deviate from this behavior owing to their capability to form hydrogen bonds with the backbone even in extended structures, whereas the solvation energy of alanine is dominated by backbone - solvent interactions.