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1.
Simulations of various beta-peptides have in the last years clarified several issues concerning peptide folding equilibria and interpretation of experimental data, especially from NMR and CD spectroscopy. These simulations involved different temperatures, pH-values, ionic strengths, solvents, and force-field parameters, but a variation of these factors for one beta-peptide has not yet been done. To investigate the influence of varying these factors, we analyze the helix stability of an all-beta3-icosapeptide bearing all 20 proteinogenic amino acid side chains, which is experimentally observed to fold into a 3(14)-helix in methanol but not in water. Structural aspects, such as hydrogen-bonded rings and salt bridges, are discussed and a comparison with NMR primary (NOE distance bounds and 3J-values) and secondary (NMR derived model structures) data is made. We further investigate the reasons for the 3(14)-helix stability/instability in methanol/water. Of all factors studied, the presence of counterions seems to be the one inducing most significant effects in the simulations. 相似文献
2.
Rashmi Tambe Shukla Naveen Kumar Yellamraju U. Sasidhar 《Journal of peptide science》2013,19(8):516-527
An important nucleation event during the folding of staphylococcal nuclease involves the formation of a β‐hairpin by the sequence 21DTVKLMYKGQPMTFR35. Earlier studies show that the turn sequence ‘YKGQP’ has an important role in the folding of this β‐hairpin. To understand the active or passive nature of the turn sequence ‘YKGQP’ in the folding of the aforementioned β‐hairpin sequence, we studied glycine mutant peptides Ac‐2DTVKLMYGGQPMTFR16‐NMe (K9G:15), Ac‐2DTVKLMYKGGPMTFR16‐NMe (Q11G:15), Ac‐2DTVKLMYGGGPMTFR16‐NMe (K9G/Q11G:15), and Ac‐2DTVKLMGGGGGMTFR16‐NMe (penta‐G:15) by using molecular dynamics simulations, starting with two different unfolded states, polyproline II and extended conformational forms. Further, 5mer mutant turn peptides Ac‐2YGGQP6‐NMe (K3G:5), Ac‐2YKGGP6‐NMe (Q5G:5), Ac‐2YGGGP6‐NMe (K3G/Q5G:5), and Ac‐2GGGGG6‐NMe (penta‐G:5) were also studied individually. Our results show that an initial hydrophobic collapse and loop closure occurs in all 15mer mutants, but only K9G:15 mutant forms a stable native‐like β‐hairpin. In the other 15mer mutants, the hydrophobic collapsed state would not proceed to β‐hairpin formation. Of the different simulations performed for the penta‐G:15 mutant, in only one simulation a nonnative β‐hairpin conformation is sampled with highly flexible loop region (8GGGGG12), which has no specific conformational preference as a 5mer. While the sequence ‘YGGQP’ in the K3G:5 simulation shows relatively higher β‐turn propensity, the presence of this sequence in K9G:15 peptide seems to be driving the β‐hairpin formation. Thus, these results seem to suggest that for the formation of a stable β‐hairpin, the initial hydrophobic collapse is to be assisted by a turn propensity. Initial hydrophobic collapse alone is not sufficient to guide β‐hairpin formation. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
3.
Agnieszka Skwierawska Joanna Makowska Stanisław Ołdziej Adam Liwo Harold A. Scheraga 《Proteins》2009,75(4):931-953
We previously studied a 16‐amino acid‐residue fragment of the C‐terminal β‐hairpin of the B3 domain (residues 46–61), [IG(46–61)] of the immunoglobulin binding protein G from Streptoccocus, and found that hydrophobic interactions and the turn region play an important role in stabilizing the structure. Based on these results, we carried out systematic structural studies of peptides derived from the sequence of IG (46–61) by systematically shortening the peptide by one residue at a time from both the C‐ and the N‐terminus. To determine the structure and stability of two resulting 12‐ and 14‐amino acid‐residue peptides, IG(48–59) and IG(47–60), respectively, we carried out circular dichroism, NMR, and calorimetric studies of these peptides in pure water. Our results show that IG(48–59) possesses organized three‐dimensional structure stabilized by hydrophobic interactions (Tyr50–Phe57 and Trp48–Val59) at T = 283 and 305 K. At T = 313 K, the structure breaks down because of increased chain entropy, but the turn region is preserved in the same position observed for the structure of the whole protein. The breakdown of structure occurs near the melting temperature of this peptide (Tm = 310 K) measured by differential scanning calorimetry (DSC). The melting temperature of IG(47–60) determined by DSC is Tm = 330 K and its structure is similar to that of the native β‐hairpin at all (lower) temperatures examined (283–313 K). Both of these truncated sequences are conserved in all known amino acid sequences of the B domains of the immunoglobulin binding protein G from bacteria. Thus, this study contributes to an understanding of the mechanism of folding of this whole family of proteins, and provides information about the mechanism of formation and stabilization of a β‐hairpin structural element. Proteins 2009. © 2008 Wiley‐Liss, Inc. 相似文献
4.
A 20‐residue peptide, IG(42–61), derived from the C‐terminal β‐hairpin of the B3 domain of the immunoglobulin binding protein G from Streptoccocus was studied using circular dichroism, nuclear magnetic resonance (NMR) spectroscopy at various temperatures and by differential scanning calorimetry (DSC). Unlike other related peptides studied so far, this peptide displays two heat capacity peaks in DSC measurements (at a scanning rate of 1.5 deg/min at a peptide concentration of 0.07 mM), which suggests a three‐state folding/unfolding process. The results from DSC and NMR measurements suggest the formation of a dynamic network of hydrophobic interactions stabilizing the structure, which resembles a β‐hairpin shape over a wide range of temperatures (283–313 K). Our results show that IG (42–61) possesses a well‐organized three‐dimensional structure stabilized by long‐range hydrophobic interactions (Tyr50 ··· Phe57 and Trp48 ··· Val59) at T = 283 K and (Trp48 ··· Val59) at 305 and 313 K. The mechanism of β‐hairpin folding and unfolding, as well as the influence of peptide length on its conformational properties, are also discussed. Proteins 2010. © 2009 Wiley‐Liss, Inc. 相似文献
5.
A 34‐residue α/β peptide [IG(28–61)], derived from the C‐terminal part of the B3 domain of the immunoglobulin binding protein G from Streptoccocus, was studied using CD and NMR spectroscopy at various temperatures and by differential scanning calorimetry. It was found that the C‐terminal part (a 16‐residue‐long fragment) of this peptide, which corresponds to the sequence of the β‐hairpin in the native structure, forms structure similar to the β‐hairpin only at T = 313 K, and the structure is stabilized by non‐native long‐range hydrophobic interactions (Val47–Val59). On the other hand, the N‐terminal part of IG(28–61), which corresponds to the middle α‐helix in the native structure, is unstructured at low temperature (283 K) and forms an α‐helix‐like structure at 305 K, and only one helical turn is observed at 313 K. At all temperatures at which NMR experiments were performed (283, 305, and 313 K), we do not observe any long‐range connectivities which would have supported packing between the C‐terminal (β‐hairpin) and the N‐terminal (α‐helix) parts of the sequence. Such interactions are absent, in contrast to the folding pathway of the B domain of protein G, proposed recently by Kmiecik and Kolinski (Biophys J 2008, 94, 726–736), based on Monte‐Carlo dynamics studies. Alternative folding mechanisms are proposed and discussed. © 2010 Wiley Periodicals, Inc. Biopolymers 93: 469–480, 2010. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com 相似文献
6.
Agnieszka Skwierawska Wioletta Żmudzińska Stanisław Ołdziej Adam Liwo Harold A. Scheraga 《Proteins》2009,76(3):637-654
Two peptides, corresponding to the turn region of the C‐terminal β‐hairpin of the B3 domain of the immunoglobulin binding protein G from Streptococcus, consisting of residues 51–56 [IG(51–56)] and 50–57 [IG(50–57)], respectively, were studied by circular dichroism and NMR spectroscopy at various temperatures and by differential scanning calorimetry. Our results show that the part of the sequence corresponding to the β‐turn in the native structure (DDATKT) of the B3 domain forms bent conformations similar to those observed in the native protein. The formation of a turn is observed for both peptides in a broad range of temperatures (T = 283–323 K), which confirms the conclusion drawn from our previous studies of longer sequences from the C‐terminal β‐hairpin of the B3 domain of the immunoglobulin binding protein G (16, 14, and 12 residues), that the DDATKT sequence forms a nucleation site for formation of the β‐hairpin structure of peptides corresponding to the C‐terminal part of all the B domains of the immunoglobulin binding protein G. We also show and discuss the role of long‐range hydrophobic interactions as well as local conformational properties of polypeptide chains in the mechanism of formation of the β‐hairpin structure. Proteins 2009. © 2009 Wiley‐Liss, Inc. 相似文献
7.
We have recently shown that two of the β‐turns (III and IV) in the ten‐stranded, β‐clam protein, cellular retinoic acid‐binding protein I (CRABP I), are favored in short peptide fragments, arguing that they are encoded by local interactions (K. S. Rotondi and L. M. Gierasch, Biochemistry, 2003, Vol. 42, pp. 7976–7985). In this paper we examine these turns in greater detail to dissect the specific local interactions responsible for their observed native conformational biases. Conformations of peptides corresponding to the turn III and IV fragments were examined under conditions designed to selectively disrupt stabilizing interactions, using pH variation, chaotrope addition, or mutagenesis to probe specific side‐chain influences. We find that steric constraints imposed by excluded volume effects between near neighbor residues (i,i+2), favorable polar (i,i+2) interactions, and steric permissiveness of glycines are the principal factors accounting for the observed native bias in these turns. Longer‐range stabilizing interactions across the β‐turns do not appear to play a significant role in turn stability in these short peptides, in contrast to their importance in hairpins. Additionally, our data add to a growing number of examples of the 3:5 type I turn with a β‐bulge as a class of turns with high propensity to form locally defined structure. Current work is directed at the interplay between the local sequence information in the turns and more long‐range influences in the mechanism of folding of this predominantly β‐sheet protein. © 2004 Wiley Periodicals, Inc. Biopolymers (Pept Sci), 2003 相似文献
8.
The β‐subunit of the human chorionic gonadotropin (hCG) hormone, which is believed to be related to certain types of cancer, contains three hairpin‐like fragments. To investigate the role of β‐hairpin formation in the early stages of the hCGβ folding, a 28‐residue peptide with the sequence RDVRFESIRLPGSPRGVNPVVSYAVALS, corresponding to the H3‐β hairpin fragment (residues 60–87) of the hCGβ subunit, was studied under various conditions using three optical spectroscopic methods: Fourier transform ir spectroscopy, electronic CD, and vibrational CD. Environmental conditions are critical factors for formation of secondary structure in this peptide. TFE : H2O mixed solvents induced helical formation. Formation of β‐structure in this peptide, which may be related to the native β‐hairpin formation in the intact hormone, was found to be induced only under conditions such as high concentration, high temperature, and the presence of nonmicellar sodium dodecyl sulfate concentrations. These findings support a protein folding mechanism for the hCGβ subunit in which an initial hydrophobic collapse, which increases intermolecular interactions in hCGβ, is needed to induce the H3‐β hairpin formation. © 1999 John Wiley & Sons, Inc. Biopoly 50: 413–423, 1999 相似文献
9.
β‐Peptides are analogs of natural α‐peptides and form a variety of remarkably stable structures. Having an additional carbon atom in the backbone of each residue, their folded conformation is not only influenced by the side‐chain sequence but also and foremost by their substitution pattern. The precise mechanism by which the side chains interact with the backbone is, however, hitherto not completely known. To unravel the various effects by which the side chains influence the backbone conformation, we quantify to which extent the dihedral angles of a β3‐substited peptide with an additional methyl group on the central Cα‐atom can be regarded as independent degrees of freedom and analyze the distributions of these dihedral angles. We also selectively capture the steric effect of substituents on the Cα‐ and Cβ‐atoms of the central residue by alchemically changing them into dummy atoms, which have no nonbonded interactions. We find that the folded state of the β3‐peptide is primarily stabilized by a steric exclusion of large parts of the unfolded state (entropic effect) and only subsequently by mutual dependence of the ψ‐dihedral angles (enthalpic effect). The folded state of β‐peptides is stabilized by a different mechanism than that of α‐peptides. Proteins 2010. © 2010 Wiley‐Liss, Inc. 相似文献
10.
The folding of the amyloidogenic H1 peptide MKHMAGAAAAGAVV taken from the syrian hamster prion protein is explored in explicit aqueous solution at 300 K using long time scale all-atom molecular dynamics simulations for a total simulation time of 1.1 mus. The system, initially modeled as an alpha-helix, preferentially adopts a beta-hairpin structure and several unfolding/refolding events are observed, yielding a very short average beta-hairpin folding time of approximately 200 ns. The long time scale accessed by our simulations and the reversibility of the folding allow to properly explore the configurational space of the peptide in solution. The free energy profile, as a function of the principal components (essential eigenvectors) of motion, describing the main conformational transitions, shows the characteristic features of a funneled landscape, with a downhill surface toward the beta-hairpin folded basin. However, the analysis of the peptide thermodynamic stability, reveals that the beta-hairpin in solution is rather unstable. These results are in good agreement with several experimental evidences, according to which the isolated H1 peptide adopts very rapidly in water beta-sheet structure, leading to amyloid fibril precipitates [Nguyen et al., Biochemistry 1995;34:4186-4192; Inouye et al., J Struct Biol 1998;122:247-255]. Moreover, in this article we also characterize the diffusion behavior in conformational space, investigating its relations with folding/unfolding conditions. 相似文献
11.
Nora Safa Jeffery C. Anderson Manibarathi Vaithiyanathan Jacob H. Pettigrew Gavin A. Pappas Dong Liu Ted J. Gauthier Adam T. Melvin 《Peptide Science》2019,111(2)
Cell penetrating peptides (CPPs) have emerged as powerful tools for delivering bioactive cargoes, such as biosensors or drugs to intact cells. One limitation of CPPs is their rapid degradation by intracellular proteases. β‐hairpin “protectides” have previously been demonstrated to be long‐lived under cytosolic conditions due to their secondary structure. The goal of this work was to demonstrate that arginine‐rich β‐hairpin peptides function as both protectides and as CPPs. Peptides exhibiting a β‐hairpin motif were found to be rapidly internalized into cells with their uptake efficiency dependent on the number of arginine residues in the sequence. Cellular internalization of the β‐hairpin peptides was compared to unstructured, scrambled sequences and to commercially available, arginine‐rich CPPs. The unstructured peptides displayed greater uptake kinetics compared to the structured β‐hairpin sequences; however, intracellular stability studies revealed that the β‐hairpin peptides exhibited superior stability under cytosolic conditions with a 16‐fold increase in peptide half‐life. This study identifies a new class of long‐lived CPPs that can overcome the stability limitations of peptide‐based reporters or bioactive delivery mechanisms in intact cells. 相似文献
12.
Larry R. Masterson Marcus A. Etienne Fernando Porcelli George Barany Robert P. Hammer Gianluigi Veglia 《Peptide Science》2007,88(5):746-753
The use of α,α‐disubstituted amino acids represents a valuable strategy to exercise conformational control in peptides. Incorporation of the nonstereogenic α‐aminoisobutyryl‐glycyl (Aib‐Gly) dipeptidyl sequence into i + 1 and i + 2 positions of an acyclic peptide sequence, originally designed and investigated by Gellman and coworkers, [H‐Arg‐Tyr‐Val‐Glu‐Val‐Yyy‐Xxx‐Orn‐Lys‐Ile‐Leu‐Gln‐NH2] nucleates a stable [2:4] left‐handed type I′ β‐turn in water. NMR spectra show that this newly designed β‐hairpin does not aggregate in water up to a concentration of ∼1 mM, and that its backbone conformation is superimposable on corresponding hairpins containing the D Pro‐Gly (literature) and Aib‐D Ala (this work) sequences. The Aib‐Gly turn‐inducer sequence eliminates complications because of cis–trans isomerization of Zzz‐Pro bonds, and constitutes an attractive alternative to the proteogenic Asn‐Gly and nonproteogenic D Pro‐Gly motifs previously suggested as turn‐inducer sequences. These design principles could be exploited to prepare water‐soluble β‐hairpin peptides with robust structures and novel function. © 2007 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 88: 746–753, 2007. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com 相似文献
13.
Model β-hairpin peptides based on variations in the turn sequence of Cochran's tryptophan zipper peptide, SWTWENGKWTWK, were studied using electronic circular dichroism (ECD), fluorescence, and infrared (IR) spectroscopies. The trpzip2 Asn-Gly turn sequence was substituted with Thr-Gly, Aib-Gly, (D)Pro-Gly, and Gly-Asn (trpzip1) to study the impact of turn stability on β-hairpin formation. Stability and conformational changes of these hairpins were monitored by thermodynamic analyses of the temperature variation of both FTIR (amide I') and ECD spectral intensities. These changes were fit to a two-state model which yielded different T(m) values, representing the folding/unfolding process, for hairpins with different β-turns. Different β-turns show systematic contributions to hairpin structure formation, and their inclusion in hairpin design can modify the folding pathways. Aib-Gly or (D)Pro-Gly sequences stabilize the turn resulting in residual Trp-Trp interaction at high temperatures, but at the same time the β-structure (cross strand H-bonds) can become less stable due to constraints of the turn, as seen for (D)Pro-Gly. The structure of the Aib-Gly turn containing hairpin was determined by NMR and was shown to be like trpzip2 (Asn-Gly turn) as regards turn and strand geometries, but to differ from trpzip1 (Gly-Asn turn). The Munoz and Eaton statistical mechanically derived multistate model, tested as an alternate point of view, represented contributions from H-bonds and hydrophobic interactions as well as conformational change as interdependent. Use of different spectral methods that vary in dependence on these physical interactions along with the structural variations provided insight to the complex folding pathways of these small, well-folded peptides. 相似文献
14.
Rajkishor Rai Srinivasarao Raghothama Rajagopalan Sridharan Padmanabhan Balaram 《Peptide Science》2007,88(3):350-361
Designed octapeptides Boc‐Leu‐Val‐Val‐Aib‐DXxx‐Leu‐Val‐Val‐OMe (DXxx = DAla, 3a; DVal, 3c and DPro, 5a ) and Boc‐Leu‐Phe‐Val‐Aib‐DAla‐Leu‐Phe‐Val‐OMe ( 3b ) have been investigated to construct models of a stable type I′ β‐turn nucleated hairpin and to generate systems for investigating helix–hairpin conformational transitions. Peptide 5a , which contains a central Aib‐DPro segment, is shown to adopt a stable type I′ β‐turn nucleated hairpin structure, stabilized by four cross‐strand hydrogen bonds. The stability of the structure in diverse solvents is established by the observation of all diagnostic NOEs expected in a β‐hairpin conformation. Replacement of DPro5 by DAla/DVal ( 3a–c ) results in sequences that form β‐hairpins in hydrogen bonding solvents like CD3OH and DMSO‐d6. However, in CDCl3 evidence for population of helical conformations is obtained. Peptide 6b (Boc‐Leu‐Phe‐Val‐Aib‐Aib‐Leu‐Phe‐Val‐OMe), which contains a centrally positioned Aib‐Aib segment, provides a clear example of a system, which exhibits a helical conformation in CDCl3 and a significant population of both helices and hairpins in CD3OH and DMSO‐d6. The coexistence of multiple conformations is established by the simultaneous observation of diagnostic NOEs. Control over stereochemistry of the central β‐turn permits generation of models for robust β‐hairpins and also for the construction of systems that may be used to probe helix–hairpin conformational transitions. © 2006 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 88: 350–361, 2007. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com 相似文献
15.
Athanassios Stavrakoudis Ioannis G. Tsoulos Zakhar O. Shenkarev Tatiana V. Ovchinnikova 《Peptide Science》2009,92(3):143-155
Arenicin‐2 is a 21 residue antimicrobial cyclic peptide, possessing one disulphide bond between residues Cys3 and Cys20. NMR and CD studies suggested that the structure of arenicin‐2 in water represented a well formed, but highly twisted β‐harpin. To investigate the spatial arrangement of the peptide side chains and to get a clear view of its possible amphipathic properties we performed molecular dynamics in explicit water. Four independent trajectories, 50 ns in length, were produced, starting from various initial conformations or by applying different simulation conditions. Arenicin‐2 retained its β‐hairpin structure during simulations, although the residues close to strand ends were found to escape from the ideal hairpin conformation. The type I′ β‐turn connecting the two strands fluctuated between type IV and II′ β‐turn. Conversely, the right‐handed twist of the β‐hairpin was well conserved with average twist value 203° ± 19° per eight residues. Several nonbonded interactions, like hydrophobic interactions between aliphatic side chains, cation/π‐aromatic interactions, CH…π aromatic bond and water bridges, contributed to the hairpin stabilization. © 2009 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 92: 143–155, 2009. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com 相似文献
16.
Chignolin is a 10-residue peptide (GYDPETGTWG) that forms a stable beta-hairpin structure in water. However, its design template, GPM12 (GYDDATKTFG), does not have a specific structure. To clarify which amino acids give it the ability to form the beta-hairpin structure, we calculated the folding free-energy landscapes of chignolin, GPM12, and their chimeric peptides using multicanonical molecular dynamics (MD) simulation. Cluster analysis of the conformational ensembles revealed that the native structure of chignolin was the lowest in terms of free energy while shallow local minima were widely distributed in the free energy landscape of GPM12, in agreement with experimental observations. Among the chimeric peptides, GPM12(D4P/K7G) stably formed the same beta-hairpin structure as that of chignolin in the MD simulation. This was confirmed by nuclear magnetic resonance (NMR) spectroscopy. A comparison of the free-energy landscapes showed that the conformational distribution of the Asp3-Pro4 sequence was inherently biased in a way that is advantageous both to forming hydrogen bonds with another beta-strand and to initiating loop structure. In addition, Gly7 helps stabilize the loop structure by having a left-handed alpha-helical conformation. Such a conformation is necessary to complete the loop structure, although it is not preferred by other amino acids. Our results suggest that the consistency between the short-range interactions that determine the local geometries and the long-range interactions that determine the global structure is important for stable tertiary structure formation. 相似文献
17.
Various strategies exist to stabilize de novo designed synthetic peptide β‐hairpins or β‐sheets structures, especially at the non‐hydrogen bonding position. However, strategies to stabilize strand termini, which are affected by fraying, are highly limited. Here, by substituting N‐terminal aliphatic amino acid with its mirror image counterpart, we achieve a significant increase in scaffold stabilization, resulting from the formation of a terminal aliphatic–aromatic hydrophobic C H…pi cluster. Our extensive solution NMR studies support the incorporation of an N‐terminal d‐ aliphatic amino acid in the design of short β‐hairpins, while successfully retaining the overall structural scaffold. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 260–266, 2016. 相似文献
18.
To investigate the effect of peptide secondary structure on proteolytic resistance, we have synthesized a series of peptides based on a well‐folded β‐hairpin, WKWK. Mutations were made within the peptide which either decreased or increased the propensity to form β‐hairpin structures and one scrambled sequence was used as an unstructured control. The peptides were incubated with three different enzymes, α‐chymotrypsin, trypsin, and pronase E, which represented both specific and non‐specific proteases. The reactions were quenched at varying time points and analyzed with RP‐HPLC to determine the rate of degradation for each of the peptides. We found that an increase in structure correlates well with an increase in resistance to degradation. We have shown that having both strong side chain interactions and a rigid D ‐Pro‐Gly β‐turn resulted in the most proteolytic resistant peptides. The results from this study suggest that β‐hairpin structure is a viable way to provide added protease resistance to a peptide. © 2009 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 92: 502–507, 2009. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com 相似文献
19.
If molecular dynamics simulations are used to characterize the folding of peptides or proteins, a wide range of conformational states needs to be sampled. This study reports an analysis of peptide simulations to identify the best methods for assessing equilibration and sampling in these systems where there is significant conformational disorder. Four trajectories of a beta peptide in methanol and four trajectories of an alpha peptide in water, each of 5 ns in length, have been studied. Comparisons have also been made with two 50-ns trajectories of the beta peptide in methanol. The convergence rates of quantities that probe both the extent of conformational sampling and the local dynamical properties have been characterized. These include the numbers of hydrogen bonds populated, clusters identified, and main chain torsion angle transitions in the trajectories. The relative equilibrium rates of different quantities are found to vary significantly between the two systems studied reflecting both the differences in peptide primary structure and the different solvents used. A cluster analysis of the simulation trajectories is identified as a very effective method for judging the convergence of the simulations. This is particularly the case if the analysis includes a comparison of multiple trajectories calculated for the same system from different starting structures. 相似文献
20.
《Peptide Science》2017,108(3)
The conformational characteristics of protected homo‐oligomeric Boc‐[β3(R)Val]n‐OMe, n = 1, 2, 3, 4, 6, 9, and 12 have been investigated in organic solvents using nuclear magnetic resonance (NMR), Fourier transform infrared (FTIR) absorption spectroscopy and circular dichroism (CD) methods. The detailed 1H NMR analysis of Boc‐[β3(R)Val]12‐OMe reveals that the peptide aggregates extensively in CDCl3, but is disaggregated in 20%, (v/v) dimethyl sulfoxide (DMSO) in CDCl3 and in CD3OH. Limited assignment of the N‐terminus NH groups, together with solvent dependence of NH chemical shifts and temperature coefficients provides evidence for 14‐helix conformation in the 12‐residue peptide. FTIR analysis in CHCl3 establishes that the onset of folding and aggregation, as evidenced by NH stretching bands at 3375 cm−1 (intramolecular) and 3285 cm−1 (intermolecular), begins at the level of the tetrapeptide. The observed CD bands, 214 nm (negative) and 198 nm (positive), support 14‐helix formation in the 9 and 12 residue sequences. The folding and aggregation tendencies of homo‐oligomeric α‐, β‐, and γ‐ residues is compared in the model peptides Boc‐[ωVal]n‐NHMe, ω = α, β, and γ and n = 1, 2, and 3. Analysis of the FTIR spectra in CHCl3, establish that the tendency to aggregate at the di and tripeptide level follows the order β > α∼γ, while the tendency to fold follows the order γ > β > α. 相似文献