Alpha-helical Chains Research Articles

Importance of eigenvector sign consistency in computations of expectation values via mixed quantum-classical surface-hopping dynamics

For simulations of systems undergoing nonadiabatic dynamics between multiple quantum states, one must often compute nonadiabatic coupling vectors, which involve the overlap of one adiabatic state with the gradient (with respect to the nuclear positions) of another. Because these states are usually computed numerically using a matrix diagonalization routine, the signs of the eigenvectors and the resulting nonadiabatic coupling vectors can change erratically over the course of a trajectory. To ensure a smooth evolution of the eigenvectors, one usually tracks the sign of the overlap of the current eigenvector with that of the previous time step and corrects the sign if needed. However, when computing time-dependent expectation values based on an ensemble of trajectories (which are typically initialized at different points in configuration space), one now has to ensure eigenvector sign continuity across the entire ensemble. In this work, we present a simple procedure for accomplishing this in mixed quantum-classical surface-hopping dynamics. The utility of this procedure is demonstrated by calculating both adiabatic state populations in a reduced model of a condensed phase proton-coupled electron transfer (PCET) reaction and subsystem state populations in an excitonic model of an alpha-helical chain undergoing vibrational energy transport (VET), using mixed quantum-classical Liouville surface-hopping dynamics. Our results show that when eigenvector sign continuity across the ensemble is neglected, as is commonly done, one can obtain large deviations from the correct values. However, after implementing this procedure, the results agree better with the exact results in the case of the PCET model and behave physically in the case of the VET model. These results illustrate the importance of a careful treatment of the signs in mixed quantum-classical dynamics calculations of expectation values in the adiabatic representation.

Synthesis and characterization of poly-l-leucine initialized and immobilized by rehydrated hydrotalcite: understanding stability and the nature of interaction

PLLs were synthesized by the ring-opening polycondensation (ROP) method using α-L-leucine N-carboxyanhydride (NCA) and initialized by triethylamine (Et3N), water or rehydrated hydrotalcite (HTrus). The role of temperature, different initiators and water in ROP was further investigated. In general, the initiators used in the polymerization reaction lead to PLL alpha-helical chains containing 5-40 monomers with NCA endgroups via a monomer-activated mechanism. However, the water has a twofold effect on ROP, as both a nucleophile and a base, which involves competition between two different types of initiating mechanisms (nucleophilic attack or deprotonation of the NCA monomer) in the polymerization reaction. This competition provides as a main product NCA endgroups with an alpha-helical structure and leads to the formation of the PLL cyclic-chains and beta-sheet structures which reduce the polymer Mw and the PD of the polypeptide. Furthermore, the water can hydrolyze the NCA endgroups resulting in PLL alpha-helical chains that contain living groups as the main product. On the other hand, the HTrus presents a double role: as both an initiator and a support. The polymers synthesized in the presence of HTrus presented a HT-carboxylate endgroup. The PLLs immobilized in HTrus through an anion-exchange method performed for just 30 minutes presented the PLL immobilized in the interlayer space of the HTrus. The PLL chains of the immobilized counterpart are stabilized by H-bonding with the M-OH of the HT structure. All the polypeptides and biohybrid materials synthesized have been characterized using different techniques (EA, ICP, XRD, Raman, MALDI-TOF, ESI-TOF, FT-IR at increasing temperatures, TG/DT analyses and TEM).

Molecular Dynamics Simulations of Apolipoprotein A-I Peptide Mimetic 4F

Coronary heart disease is the leading cause of death in the United States, claiming more lives than the next seven leading causes of death combined. High levels of high density lipoprotein (HDL) have been correlated with lower rates of coronary heart disease. Apolipoprotein A-I (apoA-I), is the principle protein in HDL, is a 243-residue class A amphipathic alpha helix capable of binding a variable number of lipid molecules. ApoA-I mimetic peptides synthesized by Anantharamaiah et al. are 18-residue class A amphipathic helices. Although they have no sequence homology to apoA-I, the peptides bind to lipids in a manner similar to that of apoA-I (i.e. antiparallel double-belt on the edge of the lipid disc). Molecular dynamics simulations of the lipid-bound peptide mimetic 4F were performed for 30 ns in explicit water using CHARMM22/27 parameters. The peptides were arranged in a stacked and staggered conformation to determine if there was any difference in the stability of the belt structure of the peptides. In the initial model, 16 straight alpha-helical chains of 4F were placed around two leaflets of 108 dimyristoylphosphatidylcholines (DMPC). In both simulations all peptides remain in contact with the lipid. The staggered model gives a more circular shape while the stacked model distorts into an oval shape. The staggered model also has a lower conformational energy than the stacked model, indicating that peptide-lipid complexes in which the peptides are staggered may be the more stable form. Salt bridge analysis shows there are three additional salt bridge interactions formed that are not present in the stacked conformation. These interactions may be a contributing factor for the more stable form of the staggered conformation.

Vibrational Analysis of Amino Acids and Short Peptides in Hydrated Media. II. Role of KLLL Repeats To Induce Helical Conformations in Minimalist LK-Peptides

Aqueous solution secondary structures of minimalist LK-peptides, with the generic sequence defined as KLL(KLLL)nKLLK, have been analyzed by means of circular dichroism (CD) and Raman scattering techniques. Our discussion in the present paper is mainly focused on four synthetic peptides (from 5 to 19 amino acids), KLLLK, KLLKLLLKLLK, KLLKLLLKLLLKLLK, and KLLKLLLKLLLKLLLKLLK, corresponding to the repeat unit, and to the peptide chains with the values of n = 1-3, respectively. CD and Raman spectra were analyzed in order to study both structural features of the peptide chains and their capability to form aggregates. On the basis of the obtained results it was concluded that the conformational flexibility of the shortest peptides (5-mer and 11-mer) is high enough to adopt random, beta-type, and helical chains in aqueous solution. However, the 11-mer shows a clear tendency to form beta-strands in phosphate buffer. The conformational equilibrium can be completely shifted to beta-type structures upon increasing ionic strength, i.e., in PBS and tris buffers. This equilibrium can also be shifted toward helical chains in the presence of methanol. Finally, the longest peptides (15-mer and 19-mer) are shown to form alpha-helical chains with an amphipathic character in aqueous solution. The possibility of bundle formation between helical chains is discussed over the temperature-dependent H-D exchange on labile hydrogens and particularly by considering the particular behavior of an intense Raman mode at 1127 cm-1 originating from the leucine residue side chain. The conformational dependence of this mode observed upon selective deuteration has never been documented up to now.

A phylogenetic analysis of cattle DRB3 alleles with a deletion of codon 65.

One of the most common cattle major histocompatibility complex DRB3 alleles, *0201, includes a deletion of codon 65 encoding one residue in the alpha-helical chain. The mutation is functionally interesting and is likely to influence peptide binding. Exon 2 of two additional del65 alleles, *3301 and *4101, have now been sequenced with the aim to investigate the evolutionary relationship of this allelic group. Despite a fairly large genetic distance between the three alleles (11-17 nucleotide substitutions causing 8-11 amino acid substitutions) we found clear indications of a common ancestry. The alpha-helical region was very similar or identical among the alleles whereas the beta-strand region was quite divergent. The results indicated that interallelic recombination has contributed to the diversification of the del65 group. Deletion of codon 65 has also been found in a roe deer DRB1 allele and a cattle DQB3 allele. Sequence comparisons of the cattle and roe deer DRB del65 alleles refuted the possibility of a trans-species persistence of a del65 allelic lineage but the two species may share a short ancestral sequence motif including del65. In addition to del65, the cattle DQB3 allele did not show any striking sequence similarities to the DRB alleles.

Formation of Parallel and Antiparallel Coiled-coils Controlled by the Relative Positions of Alanine Residues in the Hydrophobic Core

The orientation of alpha-helical chains in two-stranded coiled-coils has been shown to be determined by the presence of favorable interchain electrostatic interactions. In this study, we used de novo designed 35-residue peptides to show that when interchain electrostatic interactions are not a factor in coiled-coil formation, the relative positions of Ala residues in the middle heptad can control the parallel or antiparallel orientation of alpha-helical chains in coiled-coils. The peptides formed four-stranded coiled-coils where the helices are either all-parallel or all-antiparallel with respect to their nearest neighbor. The common structural element in these four-stranded coiled-coils is an alternating pair of Ala and Leu residues (Ala-Leu-Ala-Leu) in each of the two planes in the middle heptad. These results indicate that both the relative positions of the Ala residues in the hydrophobic core and the interchain electrostatic interactions between charged residues in the e and g positions should be considered in designing coiled-coils with the desired number of strands in the multiple-stranded assembly. These design elements are also important in orienting functional groups or domains attached to the terminals ends of a coiled-coil carrier.

The effect of pH on the folding and stability of the myosin rod.

The far-ultraviolet circular dichroism and fluorescence emission intensities of the myosin rod were studied at pH 2-11, in the absence and presence of guanidine hydrochloride. The protein kept its helicity in this pH range. Its stability in the denaturant was higher at acidic pH than at pH 7. This may be due to favorable interactions involving protonated glutamic acid residues at the interface of the two alpha-helical chains of the molecule. At alkaline pH, the fluorescence of the myosin rod was quenched, and the tryptophan region of the protein became less stable in the presence of guanidine hydrochloride, due to ionization of tyrosine residues or other amino acids close to tryptophans in the double-helix arrangement.

Characterization of a new four-chain coiled-coil: influence of chain length on stability.

Limited information is available on inherent stabilities of four-chain-coils. We have developed a model system to study this folding motif using synthetic peptides derived from sequences contained in the tetramerization domain of Lac repressor. These peptides are tetrameric as judged by both gel filtration and sedimentation equilibrium and the tetramers are fully helical as determined by CD. The four-chain coiled-coils are well folded as judged by the cooperativity of thermal unfolding and by the extent of dispersion in aliphatic chemical shifts seen in NMR spectra. In addition, we measured the chain length dependence of this four-chain coiled-coil. To this end, we developed a general procedure for nonlinear curve fitting of denaturation data in oligomeric systems. The dissociation constants for bundles that contain alpha-helical chains 21, 28, and 35 amino acids in length are 3.1 x 10(-12), 6.7 x 10(-23), and 1.0 x 10(-38) M3, respectively. This corresponds to tetramer stabilities (in terms of the peptide monomer concentration) of 180 microM, 51 nM, and 280 fM, respectively. Finally, we discuss the rules governing coiled-coil formation in light of the work presented here.

Pressure effects and thermal stability of myosin rods and rod minifilaments: fluorescence and circular dichroism studies.

In the present study hydrostatic pressure was applied upon both skeletal myosin rod molecules and rod minifilaments to learn more of the intra- and intermolecular interaction behavior of myosin. Applied pressure disassembled the rod minifilaments into individual rod molecules and dissociated each myosin rod molecule into two chains of alpha-helix. The dissociation and disassembly profiles of these systems were obtained by measuring their fluorescent anisotropy under pressure. The mid-disassembly pressure of rod minifilaments at 0.4 mg/mL concentration was 430-490 bar. However, dissociation of two helical strands of rod molecules occurred at a much higher pressure, with a mid-disassembly pressure of 1300 bar at this concentration. These results indicate that the intramolecular interactions occurring between two alpha-helical chains of a rod molecule are much more stable under pressure than the intermolecular interactions that occur among rod molecules in a minifilament. The regions in the rod molecules involved in filament assembly were investigated through usage of both the intrinsic fluorescence of tryptophan residues and the extrinsic fluorescence of 6-acryloyl-2-(dimethylamino)naphthalene (acrylodan) labeled cysteine residues. The blue spectral shifts upon minifilament formation suggest the participation of both light meromyosin (LMM) and subfragment-2 (S-2) regions of myosin rods in the filament formation. Profiles of thermal unfolding of myosin rod molecules and rod minifilaments were obtained by circular dichroism measurement. The multiple transitions exhibited upon unfolding profiles indicated the presence of more than one structural domain, each correlating with a cooperative transition. The domain transitional temperatures were found to be 1-4 degrees C higher for rods in minifilaments than those for rod molecules in a solution of similar ionic composition, indicating that all structural domains are involved in filament assembly. Furthermore, the domain transitional temperatures for rod molecules in a buffer containing 0.6 M NaCl were 6-8 degrees C higher than those for rod molecules in 5 mM sodium pyrophosphate buffer, suggesting that each structural domain of a rod molecule becomes stabilized at 0.6 M NaCl solution.

Ultimate Properties of Polymer Chains

AbstractNew polymers with exceptional properties are needed for applications in high-performance structures, novel electrical, optical and electro-optical devices, and for multi-functional smart materials. Concurrently, new computational capabilities and methods for properties prediction and analysis have enabled the study of a variety of polymer chain architectures to examine the principles that govern their high-performance properties. By semi-empirical and ab initio computational methods, flexible, stiff-chain, rigid-rod, and biological structures could be analyzed. Single chain molecular stress-strain curves for axial tension and compression were calculated, and the strain dependence of the molecular modulus and vibrational frequencies were compared to measurements of molecular deformation, such as IR and Raman spectroscopy. However, of special interest is the distinctly different response of alpha-helical biopolymer chains to strain. Indeed, in this study we compare on a theoretical basis the ‘spring-like’ microscopic mechanical response of alpha-helical biopolymers having a reinforcing intra-molecular hydrogen bonding network to analogous synthetic extended chain polymers, especially poly(para-phenylene terephthalamide) (PPTA) [KEVLARTM]. The theoretical verification of the absence of compressive buckling in alpha-helical biopolymer chains rationalizes the molecular elasticity and resistance to ‘kinking’ of those strands, manifested by the prevalence in Nature for coiled coils. The understanding of the structure-tofunction relationship in biopolymers explaining the role of the alpha-helix in these systems as a requirement for superior compressive mechanical properties, may enable new guidance for the synthesis of motifs consistent with molecular frameworks optimized by Nature.

NMR-pseudoenergy approach to the solution structure of acyl carrier protein.

A method for protein structure determination from two-dimensional NMR cross-relaxation data is presented and explored by using short amino acid segments from acyl carrier protein as a test case. The method is based on a molecular mechanics program and incorporates NMR distance constraints in the form of a pseudoenergy term that accurately reflects the distance-dependent precision of NMR cross-relaxation data. When it is used in an indiscriminant fashion, the method has a tendency to produce structures representing local energy minima near starting structures, rather than structures representing a global energy minimum. However, stepwise inclusion of energy terms, beginning with a function heavily weighted by backbone distance constraints, appears to simplify the potential energy surface to a point where convergence to a common backbone structure from a variety of starting structures is possible. In the case of the segment from residues 3 to 15 in acyl carrier protein, a nearly perfect alpha-helix is produced starting with a linear chain, an alpha-helical chain, or a chain having residues with alternating linear and alpha-helical backbone torsional angles. In the case of the segment from residues 26 to 36 a structure having a right-handed loop is produced.

Spikes and fimbriae: alpha-helical proteins form surface projections on microorganisms.

Two basic alpha-helical plans appear to characterize portions of the proteins projecting from the surface of many microorganisms. Structure A is related to that of the antibody-binding protein A of Staphylococcus aureus, in which a single polypeptide chain doubles back to form an Anti-parallel domain; the other, structure M, is related to the M proteins of group A streptococci, in which Multiple parallel alpha-helical chains interlock in a coiled-coil conformation. A projection about 100 A long may be organized on either plan, but very long projections are likely to be of the M pattern. The alpha-helical motif may account for the length of these spikes, with other functions such as anchoring or antiphagocytic activity located in domains of different structure.