Global search for minimum energy (H2O)n clusters, n = 3-5

The Gaussian-3 (G3) model chemistry method has been used to calculate the relative deltaG(o) values for all possible conformers of neutral clusters of water, (H2O)n, where n = 3-5. A complete 12-fold conformational search around each hydrogen bond produced 144, 1728, and 20,736 initial starting structures of the water trimer, tetramer, and pentamer. These structures were optimized with PM3, followed by HF/6-31G* optimization, and then with the G3 model chemistry. Only two trimers are present on the G3 potential energy hypersurface. We identified 5 tetramers and 10 pentamers on the potential energy and free-energy hypersurfaces at 298 K. None of these 17 structures were linear; all linear starting models folded into cyclic or three-dimensional structures. The cyclic pentamer is the most stable isomer at 298 K. On the basis of this and previous studies, we expect the cyclic tetramers and pentamers to be the most significant cyclic water clusters in the atmosphere.     

Density Functional Theory Study of Water Diffusion and Clustering on Pd（111）

1 INTRODUCTION The interaction of water molecules with metal sur- faces plays a vital role in a number of important pro- cesses, such as corrosion, heterogeneous catalysis, electrochemical processes in aqueous solutions, hydrogen production, etc.[1] The structure and pro- perties of water adsorbed on well-defined metal sur- faces have been the subject of numerous experi- mental and theoretical investigations. There have been a number of experimental studies of water on metal surfaces throu…     

One‐Pot Multimolecular Macrocyclization for the Expedient Synthesis of Macrocyclic Aromatic Pentamers by a Chain Growth Mechanism

POCl₃‐mediated one‐pot macrocyclization allows the highly selective formation of five‐residue macrocycles that are rigidified by internally placed intramolecular hydrogen bonds. Mechanistic investigation by using tailored competition experiments and kinetic simulation provides a comprehensive model, supporting a chain‐growth mechanism underlying the one‐pot formation of aromatic pentamers, whereby the successive addition of a bifunctional monomer unit onto either another monomer or the growing oligomeric backbone is faster than other types of bimolecular condensations involving oligomers longer than monomers. DFT calculations at the B3LYP/6‐31G* level reveal the five‐residue pentamer to be the most stable with respect to alternative four‐, six‐, and seven‐residue macrocycles. These novel mechanistic insights may become useful in analyzing other macrocyclization, oligomerization, and ploymerization reactions.     

Quantum mechanical calculations of tryptophan and comparison with conformations in native proteins

We report a detailed analysis of the potential energy surface of N-acetyl-l-tryptophan-N-methylamide, (NATMA) both in the gas phase and in solution. The minima are identified using the density-functional-theory (DFT) with the 6-31g(d) basis set. The full potential energy surface in terms of torsional angles is spanned starting from various initial configurations. We were able to locate 77 distinct L-minima. The calculated energy maps correspond to the intrinsic conformational propensities of the individual NATMA molecule. We show that these conformations are essentially similar to the conformations of tryptophan in native proteins. For this reason, we compare the results of DFT calculations in the gas and solution phases with native state conformations of tryptophan obtained from a protein library. In native proteins, tryptophan conformations have strong preferences for the beta sheet, right-handed helix, tight turn, and bridge structures. The conformations calculated by DFT, the solution-phase results in particular, for the single tryptophan residue are in agreement with native state values obtained from the Protein Data Bank.     

Conformational stability of helical peptides containing a thioamide linkage

[structure: see text] Thioxo peptide analogues of the alpha-helical peptide GCN4-p1 were synthesized and evaluated for helicity and oligomeric state. Sedimentation equilibrium and CD measurements indicate that the thioxo peptides fold into parallel alpha-helical coiled coil structures essentially identical to the native structure. This work marks the first incorporation of a thioamide linkage into the backbone of an alpha-helix and demonstrates that a thioamide linkage is compatible with positions within the helix as well as near the C-terminus.     

Statistical analysis and exposure status classification of transmembrane beta barrel residues

Several computational methods exist for the identification of transmembrane beta barrel proteins (TMBs) from sequence. Some of these methods also provide the transmembrane (TM) boundaries of the putative TMBs. The aim of this study is to (1) derive the propensities of the TM residues to be exposed to the lipid bilayer and (2) to predict the exposure status (i.e. exposed to the bilayer or hidden in protein structure) of TMB residues. Three novel propensity scales namely, BTMC, BTMI and HTMI were derived for the TMB residues at the hydrophobic core region of the outer membrane (OM), the lipid-water interface regions of the OM, and for the helical membrane proteins (HMPs) residues at the lipid-water interface regions of the inner membrane (IM), respectively. Separate propensity scales were derived for monomeric and functionally oligomeric TMBs. The derived propensities reflect differing physico-chemical properties of the respective membrane bilayer regions and were employed in a computational method for the prediction of the exposure status of TMB residues. Based on the these propensities, the conservation indices and the frequency profile of the residues, the transmembrane residues were classified into buried/exposed with an accuracy of 77.91% and 80.42% for the residues at the membrane core and the interface regions, respectively. The correlation of the derived scales with different physico-chemical properties obtained from the AAIndex database are also discussed. Knowledge about the residue propensities and burial status will be useful in annotating putative TMBs with unknown structure.     

Synthesis of Direct β‐to‐β Linked Porphyrin Arrays with Large Electronic Interactions: Branched and Cyclic Oligomers

Direct β‐to‐β linked branched and cyclic porphyrin trimers and pentamers have been synthesized by the Suzuki–Miyaura coupling of β‐borylporphyrins and β‐bromoporphyrins. The cyclic porphyrin trimer, the smallest directly linked cyclic porphyrin wheel to date, and its twined pentamer, exhibit small electrochemical HOMO–LUMO gaps, broad nonsplit Soret bands, and red‐shifted Q‐bands, thus indicating large electronic interactions between the constituent porphyrin units.     

POCl3-mediated H-bonding-directed one-pot synthesis of macrocyclic pentamers, strained hexamers and highly strained heptamers

Previously we have shown that POCl3-mediated H-bonding-directed one-pot macrocyclization allows for the highly selective preparation of five-residue macrocycles as the predominant product with low yields of hexamers and an undetectable occurrence of both tetramers and heptamers.Replacing the interiorly arrayed methyl groups with ethyl groups in these 4-7 residue macrocycles alters the relative stability order among them.Specifically,ethoxy-substituted six-residue macrocycle,rather than pentamer,turns out to be computationally the most stable,suggesting that ethoxy-containing hexamer possibly can be formed as the major product under suitable conditions.We have investigated this possibility by varying reaction temperatures and concentrations,invariably affording pentamer as the major macrocycle with strained circular hexamers and highly strained circular heptamers produced in substantial amounts.This discrepancy can be reasonably explained on the basis of bimolecular reactions between two oligomers higher than monomers via kinetic simulations.In this scenario,the acyclic pentamer is kinetically "trapped" to undergo an intramolecular cyclization to yield circular pentamer,rather than to produce acyclic hexamer.As a result,acyclic hexamer precursor is generated largely from sterically demanding bimolecular reactions between a dimer and a tetramer,or between two trimers that are kinetically slower than the pentamer-producing chain-growth reactions.We additionally found that one-pot macrocyclization proceeds to the largest extent at 40 ℃,an intriguing finding that highlights the low reactivities of acid chloride and amine groups in these H-bond-enforced acyclic oligomeric intermediates.     

Theoretical studies on the bonding and thermodynamic properties of Ge n Si m (m+n=5) clusters: the precursors of germanium/silicon nanomaterials

Theoretical studies on the Ge n Si m clusters have been carried out using advanced ab initio approaches. The lowest energy isomers were determined for the clusters with compositions n+m=2-5. All possible isomers arising due to permutations of Ge and Si atoms were investigated. The L-shaped structure for the trimers, tetragonal with diagonal bond for tetramers, and a trigonal bipyramid for pentamers represent the energy optimized ground state geometries. The bonding analyses revealed that the trimers and tetramers are stabilized through multicenter pi bonding. In pentamers, this stabilizing factor is eliminated due to the further cluster growth. The ionization of clusters does not change their geometrical characteristics. The agreement of the calculated ionization and atomization energies with those obtained from the mass spectrometric studies (through estimated appearance potential) validated the reported structures of the clusters. The bonding properties of these species are discussed using their molecular orbital characteristics and analysis of natural bond orbital population data.     

Conformational structure of some trimeric and pentameric structural units of heparin

The molecular structure of trimeric units (D-E-F and F-G-H) and the pentamer D-E-F-G-H of heparin (sodium salts and their anionic forms) was studied using the B3LYP/6-31G(d) method. The equilibrium structure of the sodium salts of the trimers and pentamer investigated in the isolated state was determined by multidentate coordination of the sodium cations with oxygen atoms of the sulfate, carboxyl, and hydroxyl (hydroxymethyl) groups, respectively. The displacement of Na+ ions from the binding sites in the sodium salt of oligosaccharides studied resulted in the appreciable change of the overall conformation of the corresponding anion. Upon dissociation, a large change in both the position of the sulfate groups and the conformation across the glycosidic bonds was observed. The stable energy conformations around the glysosidic bonds found for the pentamer investigated are compared and discussed with the available experimental X-ray structural data for the structurally related heparin-derived pentasaccharides in cocrystals with proteins.     

Absorption spectroscopy of size-selected trimers and pentamers transition metal clusters isolated in rare gas solids: preliminary steps

Size-selected positive ionic silver trimers and pentamers and nickel trimers have been codeposited, at low kinetic energy, with rare gas (Kr) onto a cold transparent surface. They have been neutralized onto the surface by electrons of few eV, with an efficiency of 80±20%. The optical absorption spectra of the resulting matrix-isolated neutral species have been recorded, with good sensitivity, in the UV-visible range. The evaporation of clusters, detected on the atom signal after deposition of Ni trimers of 20 eV, neutralized by electrons of 5 eV, is shown to be roughly 20%. This indicates that Ni₃ clusters are present in the matrix but their number is actually too low to be optically detected.     

First evidence of hexameric and heptameric ellagitannins in plants detected by liquid chromatography/electrospray ionisation mass spectrometry

Ellagitannins are bioactive plant polyphenols of which more than 500 individual compounds have been identified from plants. An ellagitannin-rich fraction was isolated by Sephadex LH-20 from Oenothera biennis (common evening primrose) leaves and roots and analysed by high-performance liquid chromatography/diode-array detection coupled to high-resolution mass spectrometry with an electrospray ionisation interface. The high-molecular mass ellagitannins were characterised by their UV spectra, molecular masses and mass spectral fragments. In addition to the previously reported dimers and trimers, an entire series of oligomeric ellagitannins from dimers to heptamers was characterised in both roots and leaves of O. biennis. This is the first report of natural ellagitannins larger than pentamers.     

The Chemistry of 2‐Alkenyl‐5(4H)‐ oxazolones. IX. Acid‐Catalyzed Oligomerization

Abstract

Results of the acid catalyzed oligomerization of 2‐alkenyl‐5(4H)‐oxazolones are reported. Employing LC–MS and preparative LC methods, the oligomeric mixtures were characterized by NMR analyses and were discovered to consist of exclusively cyclic trimers to decamers, with tetramers and pentamers predominating. A nucleophilic oligomerization mechanism involving Michael addition and C‐alkylation of a ketene‐aminal to protonated monomer was proposed that resulted in irreversible cyclization at the trimer propagation stage. Subsequent oligomerization proceeded via enolization of α‐hydrogens on 2‐substituted 5(4H)‐oxazolone products and continued Michael addition to protonated monomer. In the sense that when both enolizable hydrogens and protonated monomer are present, the oligomerization can be regarded as being “living.”     

Origin of intrinsic 3(10)-helix versus strand stability in homopolypeptides and its implications for the accuracy of the Amber force field

Current all-atom force fields often fail to recognize the native structure of a protein as the lowest free energy minimum. One possible cause could be the mathematical form of the potential based on the assumption that the conformation of a residue is independent of its neighbors. Here, using quantum mechanical (QM) methods (MP2/6-31g**//HF/6-31g** and MP2/cc-pVDZ//cc-pVDZ//HF/cc-pVDZ), the intrinsic correctness of the gas phase terms (without solvation) of the Amber ff03 and ff99 potentials are examined by testing their ability to reproduce the relative 3(10)-helix versus extended structure stabilities in the gas phase for 1-7-residue alanine, valine, leucine, and isoleucine homopolypeptides. The 3(10)-helix versus extended state stability strongly depends on chain length and less on the amino acid identity. The helical conformation becomes lower in energy than the extended conformation for all tested peptides longer than two residues, and its stability increases with the increase of chain length. The ff03 potential better describes the 3(10)-helix versus extended state energy than ff99 and also reproduces the curvature of the relative helix-extended state energies. Therefore, the mathematical form of the Amber potential is sufficient to describe the local effect of 3(10)-helix versus extended structure stabilization in the gas phase. However, the energy curves are shifted and the backbone geometries differ compared with the QM results. This may cause significant geometric discrepancies between native and predicted structures. Therefore, extant molecular mechanics force fields, such as Amber, need refinement of their parameters to correctly describe helix-extended state energetics and geometry of major conformations.     

Residue‐Specific Dynamics and Local Environmental Changes in Aβ40 Oligomer and Fibril Formation

Elucidating local dynamics of protein aggregation is crucial for understanding the mechanistic details of protein amyloidogenesis. Herein, we studied the residue‐specific dynamics and local environmental changes of Aβ40 along the course of aggregation by using para‐cyanophenylalanine (Phe_CN) as a fluorescent and vibrational probe. Our results show that the Phe_CN residues introduced at various positions all exhibited an immediate decay of fluorescence intensity, indicating a relatively synergistic process in early oligomer formation. The fast decreases in the fluorescence intensities of residues 19 and 20 in the central hydrophobic core region and residue 10 in the N‐terminal region suggest that they play crucial roles in the formation of the oligomeric core. The Phe_CN4 residue exhibits a remarkably slower decrease in fluorescence intensity, implicating its dynamic conformational characteristics in oligomer and fibril formation. Our results also suggest that the N‐terminal residues in fibrils are surrounded by a relatively hydrophobic local environment, as opposed to being solvated.     

Molecular modeling of cellulose in amorphous state. III. An innovative elastomeric crosslink system

The flexibility of molecular structures of rubber materials was evaluated using molecular modeling techniques to develop new crosslink agents which improve deformation recovery of cellulose without significant loss of the mechanical strength. Among the studied structures Poly(propylene oxide) (PPO) pentamer appears to be the most flexible and coiled one. Our calculation results showed that, cellulose crosslinked with PPO pentamers had similar deformation recovery to that crosslinked with DMDHEU. No conformation transitions were observed in these crosslinks when cellulose models were extended to 15% strain, which is consistent with the previous result that conformation transitions in crosslinks should be avoided upon extension to achieve a good recovery on crosslinked cellulose. In addition, PPO crosslinks did not significantly affect the breaking strain of cellulose based upon the cavity volume calculations, and they helped to remove the stress concentration among cellulose chains as suggested by the results of hydrogen bonding analysis. Thus, breaking strength of cellulose might not be significantly affected by PPO crosslinks as well. The preliminary experimental results confirmed above observations. Therefore, PPO pentamer appears to be a promising elastomeric backbone structure of crosslinking agents. © 2007 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 45: 1821–1833, 2007     

Inversion of the Side‐Chain Stereochemistry of Indvidual Thr or Ile Residues in a Protein Molecule: Impact on the Folding,Stability, and Structure of the ShK Toxin

ShK toxin is a cysteine‐rich 35‐residue protein ion‐channel ligand isolated from the sea anemone Stichodactyla helianthus. In this work, we studied the effect of inverting the side chain stereochemistry of individual Thr or Ile residues on the properties of the ShK protein. Molecular dynamics simulations were used to calculate the free energy cost of inverting the side‐chain stereochemistry of individual Thr or Ile residues. Guided by the computational results, we used chemical protein synthesis to prepare three ShK polypeptide chain analogues, each containing either an allo‐Thr or an allo‐Ile residue. The three allo‐Thr or allo‐Ile‐containing ShK polypeptides were able to fold into defined protein products, but with different folding propensities. Their relative thermal stabilities were measured and were consistent with the MD simulation data. Structures of the three ShK analogue proteins were determined by quasi‐racemic X‐ray crystallography and were similar to wild‐type ShK. All three ShK analogues retained ion‐channel blocking activity.     

Aromatic-aromatic interactions in proteins: beyond the dimer

Aromatic residues are key widespread elements of protein structures and have been shown to be important for structure stability, folding, protein-protein recognition, and ligand binding. The interactions of pairs of aromatic residues (aromatic dimers) have been extensively studied in protein structures. Isolated aromatic molecules tend to form higher order clusters, like trimers, tetramers, and pentamers, that adopt particular well-defined structures. Taking this into account, we have surveyed protein structures deposited in the Protein Data Bank in order to find clusters of aromatic residues in proteins larger than dimers and characterized them. Our results show that larger clusters are found in one of every two unique proteins crystallized so far, that the clusters are built adopting the same trimer motifs found for benzene clusters in vacuum, and that they are clearly nonlocal brining primary structure distant sites together. We extensively analyze the trimers and tetramers conformations and found two main cluster types: a symmetric cluster and an extended ladder. Finally, using calmodulin as a test case, we show aromatic clsuters possible role in folding and protein-protein interactions. All together, our study highlights the relevance of aromatic clusters beyond the dimer in protein function, stability, and ligand recognition.     

Inversion of the Side‐Chain Stereochemistry of Indvidual Thr or Ile Residues in a Protein Molecule: Impact on the Folding,Stability, and Structure of the ShK Toxin

ShK toxin is a cysteine‐rich 35‐residue protein ion‐channel ligand isolated from the sea anemone Stichodactyla helianthus. In this work, we studied the effect of inverting the side chain stereochemistry of individual Thr or Ile residues on the properties of the ShK protein. Molecular dynamics simulations were used to calculate the free energy cost of inverting the side‐chain stereochemistry of individual Thr or Ile residues. Guided by the computational results, we used chemical protein synthesis to prepare three ShK polypeptide chain analogues, each containing either an allo‐Thr or an allo‐Ile residue. The three allo‐Thr or allo‐Ile‐containing ShK polypeptides were able to fold into defined protein products, but with different folding propensities. Their relative thermal stabilities were measured and were consistent with the MD simulation data. Structures of the three ShK analogue proteins were determined by quasi‐racemic X‐ray crystallography and were similar to wild‐type ShK. All three ShK analogues retained ion‐channel blocking activity.