sequence-directed organization of β-peptides in self-assembled monolayers

Sequence-Directed Organization of �-Peptides in Self-Assembled Monolayers

Jagannath Mondal,† Bong June Sung,‡ and Arun Yethiraj*,†

Department of Chemistry, UniVersity of Wisconsin, Madison, Wisconsin 53706, and Department of Chemistry,Sogang UniVersity, Seoul 121-742, Republic of Korea

ReceiVed: April 10, 2009; ReVised Manuscript ReceiVed: May 14, 2009

The sequence-directed organization of self-assembled monolayers of amphiphilic �-peptides adsorbed ongold surfaces is studied using Monte Carlo simulations. A phenomenological model is presented in whicheach (helical) molecule is represented by a rigid nanorod; side groups are placed at appropriate locations.This model can distinguish between globally amphiphilic (GA) and nonglobally amphiphilic (iso-GA) sequenceisomers. The simulations show that the GA isomers have a high degree of orientational order that is notexhibited by the iso-GA isomers, which is consistent with experiment (Pomerantz et al. Chem. Mater. 2007,19, 4436). The effect of surface coverage and relative strength of electrostatic, hydrophilic, and hydrophobicinteractions on the self-assembly of �-peptides is quantified.

1. Introduction

Peptides are an attractive building block for the fabricationof nanostructured materials1-3 in which their natural tendencyto fold is exploited. R-Helical peptides2 are an attractive sec-ondary structural motif because their stable structure enablesthe design and synthesis of amphiphiles (species with segregatedhydrophilic and hydrophobic residues).4,5 Other biomimeticstructural motifs have been inspired by surfactant6,7 and blockcopolymer8 microphases.

In this article, we present a computational study of the surfaceself-assembly of a class of nonnatural peptide molecules, knownas “�-peptides”. These molecules, which are oligomers of�-amino acids,9-11 contain one more carbon atom per residuein the backbone as compared to natural peptides composed ofR-amino acids (see Figure 1). These nonnatural “foldamers”are interesting because they can show higher helical propensitythan natural peptides.12,13 In addition, the presence of two (CRand C�) carbon atoms on the backbone allows the possibilityof cyclic structures, such as trans-2-aminocyclohexane carboxy-lic acid (ACHC), in the backbone. The use of cyclicallyconstrained residues confers very high stability as well as rigidityto helical �-peptide.14,15 It is therefore possible to synthesize“nanorods” where the amphiphilic nature of the molecule canbe controlled by the sequence of amino acids.

Pomerantz et al.16-18 have investigated the sequence-directedself-assembly of �-peptides in the bulk and at surfaces. Aninteresting test sequence with dramatic sequence effects are twoisomers, “globally amphiphilic” (GA) and “nonglobally am-phiphilic” (iso-GA), of a 10-residue, 14-helical �-peptideabbreviated as �Y-(ACHC-ACHC-�K)3, where �Y and �K referto �3-homotyrosine and �3-homolysine, respectively (see Figure2). The helix adopted by this �-peptide (“14-helix”) has threeresidues per turn, and the distribution of polar and hydrophobicsites on the exterior of the molecule is controlled by thesequence. In bulk solution and at high enough concentrations,the GA isomer self-assembles into hollow tubes micrometersin length,19,20 which can form lyotropic liquid crystals.16,18 The

iso-GA isomer, however, self-assembles at most into muchsmaller globular structures. Pomerantz et al.17 studied self-assembled monolayers (SAMs) of these peptides on goldsurfaces and concluded (from ellipsometry and infrared spec-

* To whom the correspondence should be addressed. E-mail: [email protected].

† University of Wisconsin.‡ Sogang University.

Figure 1. Structure of (a) an R amino acid, (b) a � amino acid, and(c) a �-peptide residue with a cyclic ACHC group.

Figure 2. View along and perpendicular to the axis of a 14-helicalstructure of �Y-(ACHC-ACHC-�K)3 which shows how sequenceimparts amphiphilicity and sequence of isomers that are (a) globablyamphiphiic (GA) and (b) isoglobally amphiphilic (iso-GA). Color code:�K, red; ACHC, blue; �Y and backbone atoms, cyan.

J. Phys. Chem. B 2009, 113, 9379–9385 9379

10.1021/jp903341u CCC: $40.75 2009 American Chemical SocietyPublished on Web 06/22/2009

troscopy) that GA isomers formed an organized SAM, but iso-GA isomers formed a disordered SAM.

There have been a number of computational and theoreticalstudies of �-peptides, most of which have focused on modelswith atomistic detail, and of single molecules21-29 or thepotential of mean force between two molecules.30,31 Zhu et al.32,33

have developed a new force field for �-peptides that is in goodagreement with experiments for the conformations of a single�-peptide in solution. Atomistic simulations, however, are unableto reach the length scales of interest in experiment.

Self-assembled monolayers have been extensively studied34,35

using atomistic36,37 and coarse-grained lattice38 models. Thesestudies have focused on the mechanism of the adsorptionprocess,35,39-41 although there have been studies of the degreeof order.42,43 None of theses studies, however, have consideredthe effect of sequence on the self-assembly.

In this work, we study the sequence-dependent self-assemblyof �-peptides using a generic model. We model each moleculeas a nanorod, with side groups attached at appropriate locations.Monte Carlo simulations show that this model reproduces thetrends observed in experiment and provides physical insight thatcan aid the design of future experiments. We investigate theeffect of the size of side chains and their relative interactions.We conclude that the GA isomer retains an ordered SAM inmost cases. The iso-GA isomer can be less disordered if thestrength of the hydrophilic interaction is decreased and moredisordered if the strength of the hydrophobic interaction isdecreased. We use our model to make predictions on a differentsequence �Y-(ACHC-�F-�K)3 (where �F is �3-homophenyla-lanine).

The rest of the paper is organized as follows: Simulationdetails are presented in Section 2, results are presented anddiscussed in Section 3, and some conclusions are presented inSection 4.

2. Simulation Details

2.1. Molecular Model. We develop a generic model for asingle molecule based on information available from experimentand computational studies. The model consists of three features:the backbone of the helical molecule, short-ranged interactionsdue to the side groups, and a long-ranged interaction due to theelectrostatic interactions (dipole moment).

We assume that the backbone is rigid; experiments suggestthat �-peptides with cyclic residues form very stable and rigidhelices. Figure 3a depicts an atomistic description of the helixof �Y-(ACHC-ACHC-�K)3 consisting of 10 �-amino acids.

There are three amino-acid residues, ACHC, ACHC, and �K,for approximately each turn of the helix. A simplified (cartoon)version of this configuration is shown in Figure 3b, where thebackbone is represented by a cylinder and the side chains areshown as spheres. This model assumes that the residues pereach turn of the helix are located on almost the same planevertical to the principal axis of the helix, and the �3-homoty-rosine at the end of the helix can be ignored.

In the generic model, we replace the cylinder in Figure 3bwith three (hard sphere) interaction sites, and use sphericalsquare well interactions for the side chains. The model ispictorially represented in Figure 4. There are three “backbone”particles, each of which has one hydrophilic �K residue andtwo hydrophobic ACHC residues attached so that their centeris at the surface of the backbone atom. The residues are alignedon the axis of the helix and separated by equal 120° angles.The difference between the isomers is the arrangement of theside groups. In the GA isomer, the hydrophilic groups arealigned on one side of the molecule, whereas in the iso-GAisomer, each side contains only one hyrophilic group. Thearrangement of these sites is obtained from the chemicalsequence of the �-peptides.17

Excluded volume interactions appear solely through a hardsphere interaction between any two backbone sites; that is,VHS(r) ) ∞ for r < σ and VHS(r) ) 0 for r > σ. We use σ as theunit of length in this paper. The hard sphere diameter σ can becorrelated with the helical diameter of the �-peptide, which is∼5.4 Å.17 The “first” backbone bead is attached to the surfacewith its center at a distance of σ/2 from the surface.

The side groups interact via a square-well potential given by

where i and j denote side groups, kB is Boltzmann’s constant,and T is the temperature. The values of σij and εij are varied,but most of the result presented are for the values listed in Table1. We work at a fixed reduced temperature of kBT/ε ) 0.1, whereε is the unit of energy.

These numbers are motivated as follows. Since ACHC ishydrophobic residue and �K is an hydrophilic cationic residue,

Figure 3. (a) Atomistic description of a �-peptide, �Y-(ACHC-ACHC-�K)3. (b) A simplified view of the same �-peptide, where the helix ofthe peptide is represented by a cylinder and the nine side chains arerepresented by spheres.

Figure 4. Model for �-peptide �Y-(ACHC-ACHC-�K)3.

TABLE 1: Interaction Parameters for Side Groups

residue a residue b σab εab/ε

�K �K 1 4�K ACHC 0.75 4ACHC ACHC 0.5 -2

VSW,ij(r)/kBT ) εij for r < σij

) 0 otherwise(1)

9380 J. Phys. Chem. B, Vol. 113, No. 28, 2009 Mondal et al.

we use a large positive (repulsive) energy of interaction forACHC-�K and �K-�K interactions and a negative (attractive)interaction energy for ACHC-ACHC interactions. The valuesof σij reflect the relative size of the side groups. Alhough theparameters are not obtained experimentally or from an atomisticsimulation, they are chosen to reflect two crucial features ofthe residues; namely, the relative size and relative interactionsbetween the side chains.

The total short-ranged interaction, VSR, between two mol-ecules is given by

where “B” and “S” refer to “backbone” and “side-group”,respectively, and rij is the distance between sites i and j. Thesummation is restricted to prevent double-counting of interactions.

A long-range electrostatic interaction is included in additionto the short-ranged interaction above to mimic the large dipolemoment of helical �-peptides.30 The two terminal sites of thebackbone are assigned charges of -qe and qe (where e is thecharge of an electron), with the first backbone site (attached tothe surface) carrying a charge of -qe and the third backbonesite carrying a charge of +qe. The middle site is uncharged.The electrostatic interaction is taken to be truncated Coulombinteraction with a distance-dependent dielectric constant wherethe dielectric constant of the medium is assumed to be linearlyproportional to the distance, and the long-ranged interaction,VLR, takes the form

where

qie is charge of site i, and lB is the Bjerrum length. We set rc

) 4σ and q ) 1. This corresponds to a dipole moment of ∼50D, which is little larger than the dipole moment (40 D) obtainedfrom atomistic models. The magnitude of the dipole momentdoes not have a significant effect on the results. The totalinteraction between two peptides, V, is the sum of the short-ranged and the long-ranged interactions, that is, V ) VSR +VLR.

The above model is clearly very simple and has many adhoc approximations, and it is important to establish that itprovides at least a reasonable description of the interactionbetween two peptides. We validate the model via a qualitativecomparison of the potential of mean force between twomolecules to that obtained from atomistic simulations. Thepotential of mean force, W, is give by

where V is the interaction potential between two peptides and⟨...⟩ denotes an ensemble average over configurations for a fixedcenter-of-mass distance.

The potential of mean force is depicted in Figure 5 for theGA isomer for four cases: with the two molecules aligned eitherside-to-side or head-to-head, and in each case with the dipolemoments aligned either in a parallel or antiparallel configuration.The qualitative behavior is similar to that reported by Miller etal.30 Note that there is a strong attractive interaction in the side-to-side configuration at short distances, and this interaction isdominated by the short-ranged square-well interactions. The(electrostatic) interaction in the head-head configuration ismuch weaker and occurs at a larger center-of-mass distancebecause of the geometry of the molecules.

2.2. Monte Carlo Simulation Method. Initial configurationsare prepared by grafting the peptides to the surface. A two-dimensional lattice of desired dimensions is prepared to mimicthe (111) surface of gold. Peptide molecules are sequentiallyattached to the surface as follows: A lattice point is chosen atrandom, and an attempt is made to attach a peptide with itsaxis normal to the surface. The attempt is accepted if theconfiguration is free of overlap and rejected otherwise. Onethousand peptides are used in the simulations and the simulationcell has lateral dimensions of 53.425 σ × 46.268 σ (withperiodic boundary conditions in both directions) for a surfacecoverage of 0.32. Chemical interactions between the gold surfaceand the peptide are neglected; that is, the surface is impenetra-ble and interacts via a hard-sphere interaction with the backboneatoms. The hard sphere diameter between the surface and thebackbone atom is 0.76σ, which is the mean of the backbonediameter of σ and the diameter of a gold atom of 0.533σ (0.288nm). Once the initial configuration has been created, for thepurposes of the simulation, the surface is treated as a continuum.

The simulation proceeds by moving a single peptide via eithertranslation or rotation (in two directions) about the fixed site.The use of a translational move is supported by the mobility ofpeptides on a gold surface.44-47 For alkanethiol SAM phases, ithas recently been suggested that gold-thiol-alkane moietiesmove together on the surface.47 Our coarse-grained model doesnot have the resolution to distinguish between the molecules’moving and a complex’s moiety moving. We note also that useof a Monte Carlo method precludes an investigation of thedynamic properties. The translational move is accepted accord-ing to the Metropolis criterion. The system is assumed to beequilibrated if the internal energy has reached a steady value(∼5 × 107 attempted moves). Once the system is equilibrated,

VSR ) ∑i,j∈B

VHS(rij) + ∑i,j,∈S

VSW,ij(rij) (2)

VLR ) ∑i,j∈B

Vel,ij(rij) (3)

Vel,ij(r)/kBT )qiqjlB

σ (σ2

r2- σ2

rc2) r e rc

) 0 otherwise

(4)

WkBT

) -ln⟨exp(- VkBT)⟩ (5)

Figure 5. Potential of mean force for four different orientations wherer is the distance between the centers of mass of two peptides.

Sequence-Directed Organization of �-Peptides J. Phys. Chem. B, Vol. 113, No. 28, 2009 9381

we calculate average properties over a trajectory of 5 × 107

attempted moves. Properties are averaged over 5 independenttrajectories, starting with different initial configurations.

3. Results and Discussion

The main result of the paper is that the GA isomerspreferentially align perpendicular to the surface and organizemore efficiently than the iso-GA isomers. The orientation of apeptide with the surface is characterized by the angle, γ, betweenthe axis of the molecule and the surface normal; γ ) 0corresponds to vertical alignment and γ ) 90° corresponds tothe molecule lying flat on the surface. The mutual orientationof two peptides is characterized by the angle µ between theiraxes with µ ) 0 corresponding to two aligned molecules. Figure6 depicts the probability distribution function for µ and γ (inset),for the GA and iso-GA isomers, for a surface coverage of 0.32.The GA isomers are significantly more aligned with the surfacenormal than the iso-GA isomers and also more aligned witheach other. In addition, the distribution of angles is much sharperfor the GA isomers than for the iso-GA isomers, whichestablishes that the GA isomers are more ordered on the surface.These two features qualitatively support the experimentalobservation17 that the organization of a SAM of the GA isomeris highly ordered.

A direct comparison with experiment is not possible becausethe degree of order is inferred rather than measured in theexperiments. In the experiments,17 the degree of order isestimated from the smide I/ smide II ratios obtained frominfrared spectroscopy. This ratio for the self-assembled mono-layer of two isomers is compared to that of a powder state ofthe same isomer. For the GA isomer, they find that the ratiofor the self-assembled monolayer is very different from apowdered state, and hence, they conclude that the GA isomeris highly ordered. In the simulations, we can directly measurethe degree of order, which we report as P(γ) or P(µ), but cannotquantitatively compare this to experiment, which does notprovide a direct measure of the orientational order.

The monolayer thickness, obtained from the ensemble-averaged height of the third backbone particle from the surface,is 1.44 ( 0.15 nm for the GA monolayer and 1.27 ( 0.17 nmfor the iso-GA monolayer (with σ ) 0.54 nm). Although theiso-GA monolayer is thinner, the difference is not statisticallysignificant.

In the experiments,17 the estimated thickness of the monolayer(obtained from ellipsometry) depended on the nature of attach-ment of the peptides to the surface. GA and iso-GA peptidesattached with an N-terminal thiol group showed the same filmthickness, but chemisorbed films of iso-GA peptides werethicker than than those of the GA isomers (1.5 ( 0.1 nmcompared to 1.2 ( 0.1 nm). This discrepancy could be becausein the experimental system, the interaction of the peptides withthe gold surface causes the ordered layers to lie at an angle tothe normal that is different from 0°, and this interaction hasnot been included in the model. As pointed out by Pomerantzet al.,17 the orientation of the peptides cannot be inferred fromthe ellipsometry data, and the source of this discrepancy betweenthe model and experiment remains a speculation.

In addition to the orientational organization, the GA isomersappear to be spatially ordered. Figure 7 shows a snapshot froma final configuration of monolayers GA and iso-GA isomers.In the snapshot of the GA molecules, there is a predominanceof chains of molecules, which give the configuration a mazelikeappearance. In contrast, the snapshot of the iso-GA moleculesshows liquidlike disorder. The GA isomers preferentially interactvia hydrophobic contacts, and this supports a strong alignment

Figure 6. Probability distribution function(P(µ)) for the angle betweenthe axis of two peptides. Inset: probability distribution function, (P(γ)),the angle between the peptides and the surface normal.

Figure 7. Final configuration of monolayers of (a) GA and (b) iso-GA isomers for a surface coverage of 0.32. Color code: ACHC, blue;�K, red; backbone, cyan.


of the molecules. This hydrophobic interaction also promoteschain formation, which results in the spatial order observed inFigure 7. We are not aware of experimental observations thatcan address this difference in order.

The effect of the short-ranged interactions on the alignmentand lateral order can be understood by considering the differencein the energy of a pair of molecules as a function of their relativeorientation (see Figure 8). For the GA isomer, when twomolecules are parallel, all the hydrophobic groups can align,and this gives an energy of -6kBT. For the iso-GA isomer, atleast one of the pair interactions is repulsive, and this makesthe parallel configuration less favorable than a configuration inwhich one of the molecules is tilted. For example, if the �Kgroup is in the second position (as shown in Figure 8), then theenergy is +4kBT, but tilting one of the molecules reduces thisunfavorable interaction while inducing an attraction betweenhydrophobic groups and has an energy of -2kBT. Since thereare six different choices for positions of �K groups in a pair ofpeptides, the number of favorable angles is large, and this resultsin orientational disorder.

A decrease in the surface coverage decreases the degree ofmolecular alignment of the GA, but not the iso-GA isomers.One would expect that increasing the surface coverage will resultin an increase in the alignment of both GA and iso-GA isomers,and indeed, we do observe this. In the range of surface coveragebetween 25% and 35%, we find that decreasing the surfacecoverage has a marked impact on the alignment of the GAisomers. As the surface coverage is decreased, the unfavorabledipole-diple interactions cause the alignment of the moleculesto decrease, although the most probable angle (i.e., peak in theµ distribution function) is unchanged. The effect is dramatic:the value of the peak in P(µ) for the GA isomer drops from0.08 to 0.03 as the surface coverage is decreased from 0.32 to0.24. This is compensated for by a fairly uniform increase inP(µ) for other angles. Interestingly, the magnitude of the peakP(µ) does not change significantly with surface coverage forthe iso-GA isomers, although the position shifts to higher angles.

There are many parameters in our generic model, and it isimportant to judge how they affect the qualitative featurespredicted. In particular, it is interesting to investigate the effectof the magnitude of the dipole moment and the strength andrange of the short-ranged interactions.

The value of the dipole moment is not a significant factor atexperimentally relevant values of the surface coverage. Decreas-

ing the dipole moment increases the degree of alignment of theGA isomers while having little effect on the alignment of theiso-GA isomers. The effect is more significant at low surfacecoverage, where the molecules have the free volume to lie flaton the surface.

The strengths of the hydrophobic and hydrophilic interactionshave little impact on the alignment of the GA isomers, but asmaller hydrophilic interaction strength or larger hydrophobicinteraction strength slightly increases the alignment of the iso-GA isomers. These trends can be explained using the geometricarguments presented in the discussion related to Figure 8. Thecanonical set of parameters is ε�K,�K ) ε�K,ACHC ) 4 andεACHC,ACHC ) -2. Figures 9a and b depict the probabilitydistribution function for the angle µ for the GA and iso-GAisomers for ε�K,�K ) ε�K,ACHC ) 4, εACHC,ACHC ) -1 and -3,and εACHC,ACHC ) -2, ε�K,�K ) ε�K,ACHC ) 2 and 5, respectively.

Figure 9a and b shows that the alignment of the GA isomersis relatively insensitive to the strength of the hydrophobic orhydrophilic interactions. This is expected because the strengthof the interactions does not change the most favorable anglefor the lowest energy state (see Figure 8). Increasing the strengthof the hydrophobic attraction (Figure 9a) or decreasing thestrength of the hydrophilic repulsion (Figure 9b) increases thealignment of the iso-GA isomers. This is also reasonable becauseboth of these changes tend to bring the molecules closer to eachother, and this naturally leads to a greater alignment of themolecules.

The sizes of the hydrophilic and hydrophobic groups do nothave a significant effect on the alignment of the isomers. Thecanonical set of parameters is σ�K ) 1 and σACHC ) 0.5, withthe mixing rule σ�K,ACHC ) (σ�K + σACHC)/2. We investigatethe probability distribution function for the angle γ for the GAand iso-GA isomers for σ�K ) 1; σACHC ) 0.4, 0.5, and 0.6;and σACHC ) 0.5; and σ�K ) 0.9, 1, and 1.1 and find that therelative behavior of the peptides is insensitive to the values ofthese parameters. In all cases, P(µ) is quite similar, except thatfor the GA isomer, increasing the size of the hydrophobic groupresults in an extra population at a higher angle. We interpretthis second peak as follows: The increase in σACHC provides anattractive interaction between the GA isomers at a largerdistance, and the peptide can then decrease the repulsiveelectrostatic interaction by deviating from a parallel orientation.To verify our hypothesis, we have performed simulations at a

Figure 8. Effect of relative orientation on the energies of the different isomers where the larger (red) side groups are hydrophilic and smaller sidegroups (blue) are hydrophobic. For the GA isomer (left) the parallel orientation of them is favorable. For the iso-GA isomer, the parallel configuration(middle) results in repulsive overlap of the hydrophilic sites and is therefore not as favorable as a tilted configuration (right) in which the smallerhydrophobic sites overlap.


higher surface area coverage and found the intensity of the extrapopulation is reduced.

Another sequence of interest is �Y-(ACHC-�F-�K)3, where�F is �3-homophenylalanine. Solutions of this sequence in thebulk display behavior that is in some ways exactly the oppositeof �Y-(ACHC-ACHC-�K)3: for �Y-(ACHC-ACHC-�K)3, theGA isomer displays liquid crystalline phases and the iso-GAisomer does not, but for �Y-(ACHC-�F-�K)3, the iso-GA isomerdisplays a liquid crystalline phase and the GA isomer does not.18

We model �Y-(ACHC-�F-�K)3 in a fashion identical toY-(ACHC-ACHC-�K)3 except that the size of the �F group is1.0; that is, larger than σACHC. Our simulations show (not shown)that for the surface assembly, the trend displayed by �Y-(ACHC-�F-�K)3 is identical to that seen for �Y-(ACHC-ACHC-�K)3; that is, the GA isomer is more ordered than the iso-GAisomer. This prediction could be tested via experiments. Thisis a surprising result because for the bulk solution, the trendfor �Y-(ACHC-�F-�K)3 is the opposite of that for �Y-(ACHC-ACHC-�K)3; that is, the iso-GA form of �Y-(ACHC-�F-�K)3

displays liquid crystalline phases and the GA form does not.

4. Conclusions

We study the sequence-dependent self-assembly of �-peptideson a gold surface using a generic rigid model for the molecules,

which are represented by rigid tangent shish-kabob trimers withhydrophobic and hydrophilic groups attached at appropriatelocations. The model predicts that the globally amphiphilicisomer (GA) forms an ordered self-assembled monolayer,whereas the isomer that is not amphiphilic (iso-GA) forms adisordered self-assembled monolayer. The model containsinteraction parameters that are assigned in a somewhat ad hocfashion, but the predictions are quite robust and do not changein any significant fashion if the values of the parameters arechanged by (20%. These predictions are in qualitative agree-ment with experiments17 on isomers of �Y-(ACHC-ACHC-�K)3. The model suggests that the degree of alignment of theiso-GA molecules can be tuned by a change in hydrophobicityand hydrophilicity, but the self-assembled monolayer of GAisomers always shows a high degree of order.

The simulations show that the sequence-dependent assemblyof molecules can be qualitatively captured and understood usingrather crude models. There are also many interesting experimentsrelated to the behavior of the same �-peptides in solution. Itwould be interesting to see if these simple models can shedlight on the mechanism of tube formation in �-peptides. Worktoward this end is in progress.

Acknowledgment. This research was supported by UW-Madison Nanoscale Science and Engineering Center (NSF GrantDMR-0425880).

References and Notes

(1) Slocik, J. M.; Tam, F.; Halas, N. J.; Naik, R. R. Nano Lett. 2007,7, 1054.

(2) Rydanov, M. G. Biochem. Soc. Trans. 2007, 35, 487.(3) Valery, C.; Paternostre, M.; Robert, B.; Gulik-Krzywicki, T.;

Narayanan, T.; Dedieu, J.; Keller, G.; Torres, M.; Cherif-Cheikh, R.; Calvo,P.; Artzner, F. Proc. Natl. Acad. Sci., U.S.A. 2003, 100, 10258.

(4) Yu, Y.; Berndt, P.; Tirrell, M.; Fields, G. B. J. Am. Chem. Soc.1996, 118, 12515.

(5) Vauthey, S.; Santoso, S.; Gong, H.; Watson, N.; Zhang, S. Proc.Natl. Acad. Sci., U.S.A 2002, 99, 5355.

(6) Lu, J. R.; Zhao, X. B.; Yaseen, M. Curr. Opin. Colloid InterfaceSci. 2007, 12, 60.

(7) Berti, D. Curr. Opin. Colloid Interface Sci. 2006, 11, 74.(8) Borner, H. G.; Schlaad, H. Soft Matter 2007, 3, 394.(9) Cheng, R. P.; Gellman, S. H.; Degrado, W. F. Chem. ReV. 2001,

101, 3219.(10) Gellman, S. H. Acc. Chem. Res. 1998, 31, 173.(11) Hill, D. J.; Mio, M. J.; Prince, R. B.; Hughes, T. S.; Moore, J. S.

Chem. ReV. 2001, 101, 3893.(12) Appella, D. H.; Barchi, J. J., Jr.; Durell, S. R.; Gellman, S. H. J. Am.

Chem. Soc. 1999, 121, 2309.(13) Raguse, T. L.; Lai, J. R.; Gellman, S. H. J. Am. Chem. Soc. 2003,

125, 5592.(14) Appella, D. H.; Christianson, L. A.; Karle, I. L.; Powell, D. R.;

Gellman, S. H. J. Am. Chem. Soc. 1999, 118, 13071.(15) Appella, D. H.; Christianson, L. A.; Klein, D. A.; Richards, M. R.;

Powell, D. R.; Gellman, S. H. J. Am. Chem. Soc. 1999, 121, 7574.(16) Pomerantz, W. C.; Abbott, N. L.; Gellman, S. H. J. Am. Chem.

Soc. 2006, 128, 8730.(17) Pomerantz, W. J.; Cadwell, K. D.; Hsu, Y.; Gellman, S. H.; Abbott,

N. L. Chem. Mater. 2007, 19, 4436.(18) Pomerantz, W. C.; Yuwono, V. M.; Pizzey, C. L.; Hartgernik, J. D.;

Abbott, N. L.; Gellman, S. H. Angew. Chem. Int. Ed. 2008, 47, 1.(19) Raguse, T. L.; Lai, J. R.; Leplae, P. R.; Gellman, S. H. Org. Lett.

2001, 3, 3963.(20) Pizzey, C. L.; Pomerantz, W. C.; Sung, B. J.; Yuwono, V. M.;

Gellman, S. H.; Hartgernik, J. D.; Yethiraj, A.; Abbott, N. L. J. Chem.Phys. 2008, 129, 095103.

(21) Wu, Y. D.; Wang, D. P. J. Am. Chem. Soc. 1998, 120, 13485.(22) Daura, X.; van Gunsteren, W. F.; Mark, A. E. Proteins: Struct.

Funct. Genet. 1999, 34, 269.(23) Daura, X.; Gademann, K.; Schafer, H.; Jaun, B.; Seebach, D.; van

Gunsteren, W. F. J. Am. Chem. Soc. 2001, 123, 2393.(24) Schafer, H.; Daura, X.; van Gunsteren, W. F. Proteins: Struct.

Funct. Genet. 2001, 43, 45.(25) Glattli, A.; Seebach, D.; van Gunsteren, W. F. HelV. Chim. Acta

2004, 87, 2487.

Figure 9. Effect of the strength of hydrophobic and hydrophilicinteractions on the alignment of the molecules. Comparison of theprobability distribution function of the angle of the peptide with thesurface normal for (a) ε�K,�K ) ε�K,ACHC ) 4 for various values ofεACHC,ACHC (as marked) and (b) εACHC,ACHC ) -2 for various values ofε�K,�K () ε�K,ACHC), as marked.


(26) Mohle, K.; Gunther, R.; Thormann, M.; Sewald, N.; Hofmann, H.-J. Biopolymers 1999, 50, 167.

(27) Gunther, R.; Hoffman, H. J. HelV. Chim. Acta 2002, 85, 2149.(28) Jorgensen, W. L.; Maxwell, D. S.; Tirado-Rives, J. J. Comput.

Chem. 2001, 22, 1646.(29) Rathore, N.; Gellman, S. H.; de Pablo, J. J. Biophys. J. 2006, 91,

3425.(30) Miller, C. A.; Hernandez-Ortiz, J. P.; Abbott, N. L.; Gellman, S. H.;

de Pablo, J. J. J. Chem. Phys. 2008, 129, 015102.(31) Miller, C. A.; Abbott, N. L.; Gellman, S. H.; de Pablo, J. J. Biophys.

J. 2008, 95, 3123.(32) Zhu, X.; Yethiraj, A.; Cui, Q. J. Chem. Theory Comput. 2007, 3,

1538.(33) Zhu, X.; Konig, P.; Gellman, S. H.; Yethiraj, A.; Cui, Q. J. Phys.

Chem. B 2008, 112, 5439.(34) Hautman, J.; Bareman, J. P.; Mar, W.; Klein, M. L. J. Chem. Soc.

Faraday Trans. 1991, 87, 2031.(35) Neves, R. S.; Motheo, A. J.; Silva Fernandes, F. M. S.; Fartaria,

R. P. S. J. Braz. Chem. Soc. 2004, 15, 224.(36) Raut, V. P.; Agashe, M. A.; Stuart, S. A.; Latour, R. A. Langmuir

2005, 21, 1629.

(37) Agashe, M. A.; Raut, V. P.; Stuart, S. A.; Latour, R. A. Langmuir2005, 21, 1103.

(38) Wijmans, C. M.; Linse, P. J. Phys. Chem. 1996, 100, 12583.(39) Zhan, Y.; Mattice, W. L.; Napper, D. H. J. Phys. Chem. 1993, 98,

7502.(40) Zhan, Y.; Mattice, W. L.; Napper, D. H. J. Phys. Chem. 1993, 98,

7508.(41) Pertsin, A. J.; Grunze, M. C. Langmuir 2000, 16, 8829.(42) Zhao, X.; Leng, Y. S.; Cummings, P. T. Langmuir 2006, 22, 4116.(43) Gronbech-Jensen, N.; Parikh, A. N.; Beardmore, K. M.; Dasai, R. C.

Langmuir 2003, 19, 1474.(44) Mulhereran, P.; Pellenc, D.; Bennett, R. A.; Green, R. J.; Sperrin,

M. Phys. ReV. Lett. 2008, 100, 068102.(45) Tilton, R. D.; Gast, R. P.; Robertson, C. R. Biophys. J. 1990, 58,

1321.(46) Tilton, R.; Robertson, C. R.; Gast, R. P. J. Colloid Interface Sci.

1990, 137, 1.(47) Yu, M.; Bovet, N.; Satterley, C. J.; Bengio, S.; Lovelock, K. R. J.;

Milligan, P. K.; Jones, R. G.; Woodruff, D. G.; Dhanak, V. Phys. ReV.Lett. 2006, 97, 166102.

JP903341U


sequence-directed organization of β-peptides in self-assembled monolayers

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