Dipeptides Embedded in a Lipid Bilayer Membrane as Synthetic Water

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Dipeptides Embedded in a Lipid Bilayer Membrane as Synthetic Water Channels Xian KONG, Zeyu Zhao, and Jianwen Jiang Langmuir, Just Accepted Manuscript • DOI: 10.1021/acs.langmuir.7b02060 • Publication Date (Web): 21 Jul 2017 Downloaded from http://pubs.acs.org on July 25, 2017

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Dipeptides Embedded in a Lipid Bilayer Membrane as Synthetic Water † Channels Xian Kong, Zeyu Zhao, Jianwen Jiang* Department of Chemical and Biomolecular Engineering, National University of Singapore, 117576, Singapore

Abstract Water channels are essential to life sciences and many biological processes. We report

a

molecular

simulation

study

on

dipeptides

embedded

in

a

lipid

(dipalmitoylphosphatidylcholine) membrane as synthetic water channels. Five dipeptides are examined including FF, FL, LF and LL (with hydrophilic channels) and AV (with hydrophobic channel). It is found that AV is unstable in the lipid membrane due to incompatible interaction between the hydrophilic external surface of AV and the hydrophobic lipid tails; whereas FF, FL, LF and LL with hydrophobic external surface exhibit good stability. In the four hydrophilic channels FF, FL, LF and LL, water chains are formed; the number of chains ranges from multiple, two to one depending on channel diameter; moreover, water undergoes single-file diffusion and the mobility is enhanced with increasing channel diameter. The permeation rate of water in FF channel is 9.20/ns, about three times of that in aquaporin; however, the rate in FL, LF and LL is much slower. Intriguingly, the rate can be tuned by a lateral stress/strain on the lipid membrane. The simulation study provides fundamental understanding on the stability of dipeptide channels embedded in a lipid membrane, quantitatively characterize water structure, dynamics and permeation in the channels. These microscopic insights are useful for the development of new water channels.

Keywords: Dipeptides, lipid membrane, molecular simulation, stability, water permeation

*Corresponding author: [email protected] †

This work is dedicated to Prof. Keith E. Gubbins on the occasion of his 80th birthday. 1

ACS Paragon Plus Environment

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1. Introduction Water transport through the cell membrane is essential to living cells; however, it is energetically unfavorable due to the presence of hydrophobic lipid tails.1 There are natural water channels, e.g. aquaporin2,3 and gramicidin A,4 existing in the cell membrane to facilitate water transport. A series of studies have been dedicated to elucidate the mechanism of water transport in these channels.5 On the other hand, synthetic water channels have been proposed such as carbon nanotubes,6 peptide channels,7 pillar arenes,8 etc. As readily available and biologically compatible compounds, dipeptides can self-assemble to form crystals that contain one dimensional (1D) straight channels.9,10 The channel diameter ranges from 3 to 10 Å, implying the potential in adsorption, transport and molecular level separation. There are two classes of dipeptide channels: hydrophobic Val-Ala (VA) and hydrophilic Phe-Phe (FF). The VA class channels are formed through a 3D hydrogen bond network by dipeptides with two fairly small side chains like Val-Ala, Ala-Val, Val-Val, and Ala-Ile,11-14 in which the side chains constitute the hydrophobic inner surface. By contrast, the FF class channels are formed by dipeptides with large side chains commonly from Phe and Leu. The structure is maintained by an 1D hydrogen bonds and side chain packing, nevertheless, the side chains are not located in the inner surface rendering the hydrophilicity of the channels.15 A handful of studies have been reported on dipeptide materials. For instance, high adsorption capacity of Xe in AV and VA crystals was experimentally determined.16 VA, AV, IV and VI crystals containing various nanochannels were tested for the storage of CH4, CO2 and H2.17 Extremely high selectivities for O2/N2 and O2/Ar, well above those of polymeric and 2


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carbonaceous materials, were experimentally observed in AA crystal.18 Water confined in tryptophylglycine (WG) channel was simulated by molecular dynamics (MD) technique. Upon temperature increasing from 40 to 388 K, several water phases in the WG channel were identified including crystalline, amorphous, liquid-like, liquid and superheated phases. At 300 K, the diffusion coefficient of confined water was estimated to be 4.6×10-6 cm2s-1, comparable with those in other synthetic water channels.19 Proton transport was found to be facilitated by porous dendritic dipeptides through a Grotthuss mechanism, while impeding Li+, Na+ and Cl− transport.20 Due to the special arrangement of side chains resulting in 1D hydrophobic and hydrophilic channels, dipeptides might be superior for water transport and act as synthetic channels. In this study, we embed five different dipeptide channels into a lipid bilayer membrane, investigate their stability and water transport using molecular dynamics simulations. This type of study is of central importance to provide fundamental insight into water transport in dipeptide channels and explore the possibility of using dipeptides as synthetic water channels. Following this introduction, the models of five dipeptides and lipid are briefly described in Section 2; the simulation methods are also outlined. In Section 3, the stability of dipeptide embedded lipid membrane is first examined, then water structure, dynamics and permeation through the channels are quantified. Finally, concluding remarks are summarized in Section 4.

2. Models and methods Five dipeptide channels are examined including one hydrophobic Ala-Val (AV),13 and four hydrophilic Phe-Phe (FF), Phe-Leu (FL), Leu-Phe (LF), Leu-Leu (LL).15 The channels were 3


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constructed from the experimental X-ray crystallographic data. Table 1 lists the channel diameters and lengths used in this study. The diameters were estimated using crystalline structures by the HOLE program.21 The lipid is dipalmitoylphosphatidylcholine (DPPC), which is a major component of cell membrane. For the five dipeptide channels, their lengths are comparable to the DPPC membrane with a thickness of approximately 3.5 nm. The dipeptides were described by the Optimized Potentials for Liquid Simulations all atom (OPLS-AA)22 force field and the DPPC by the reparametrized Berger’s model.23

Table 1. Diameters and lengths of dipeptide channels. Dipeptide

Diameter (nm)

Length (nm)

FF

0.92

3.1

FL

0.42

3.3

LF

0.35

3.2

LL

0.32

3.3

AV

0.50

3.4

Figure 1. Initial configuration of a simulation system with FF channel embedded in the lipid membrane. (a) side view and (b) top view. The lipids are represented by pink lines and the phosphate atoms by yellow spheres. Dipeptides are in green and water molecules are in red (atom O) and gray (atom H). In (b), water molecules are omitted for clarity.

4


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Figure 1 shows a typical simulation system with the FF channel embedded in the lipid membrane and solvated by water. The three point potential (TIP3P) model was used to mimic water.24 After the initial configuration, the system was energy minimized using the steepest descent optimization. Then, 10 ns equilibrium MD simulation was conducted with the dipeptide positions restrained by a force constant of 1000 kJ/(mol·nm2). During the equilibration process, water permeated into the channel forming water chain(s). Finally, 50 ns production MD simulation without position restrain was performed. The temperature was at 310 K monitored by the Nose-Hoover thermostat25 with a coupling constant of 0.2 ps. The pressure was controlled by the Berendsen algorithm26 with a coupling constant of 2.0 ps. Specifically, the pressure along the z direction was at 1 bar, while in the xy direction it was maintained by a surface tension. In this context, the simulation was conducted in a NPzγT ensemble (N is the number of atoms in the system, Pz is the pressure in the z direction, γ is the surface tension in the xy direction, and T is temperature).27 The lipid membrane may undergo structure change upon lateral stress/strain, thus different surface tensions common in physiological environment were considered. For each case, three independent simulations were carried out. A cutoff of 1.2 nm was used to calculate the Lennard-Jones and short-range electrostatic interactions, while the long-range electrostatic interactions were evaluated by the particle-mesh Ewald method28 with a grid spacing of 0.12 nm. The time step used for integration was 2 fs. All the simulations were performed using GROMACS v.5.0.6.29 The simulation results were analyzed by in-house developed codes. During analysis, the system at each time framework was rotated or translated to keep the position of dipeptide channel close to its initial configuration.

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3. Results and Discussion 3.1 Stability of dipeptide channels Dipeptide channels are assembled through non-covalent interactions and they may disassemble upon external stimulus. Thus, it is intriguing to examine their stability in the lipid membrane. Figure 2 plots the root mean-squared deviations (RMSDs) of the main chain atoms of five dipeptide channels. Apparently, the hydrophobic channel AV is unstable when embedded in the lipid membrane, as seen from its rapid increase of RMSD. This is because the external surface of AV channel is hydrophilic and unfavorable to reside in a highly hydrophobic environment of the lipid bilayer. The final structure of the AV channel is shown in Figure 3, several AV molecules are find to dissemble from the channel into bulk water and the channel collapses to a certain extent.

1.5

RMSD (nm)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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FF FL LF LL LL' AV

1.0

0.5

0.0

0

10

20

30

40

50

t (ns) Figure 2. RMSDs of different channels. FF, FL, LF, LL, AV are for all the dipeptide molecules in the system. LL’ represents the LL molecules in the membrane excluding the one exfoliated from the channel.

6


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By contrast, FF, FL and LF channels maintain their original structures in the lipid membrane despite slight tilting (see Figure 3). This is attributed to the favorable interaction between the hydrophobic external surface of FF, FL and LF with the hydrophobic lipid. The RMSDs are small of about 0.12 nm and remain nearly a constant over 50 ns duration, except a small rise in the RMSD of FL after 30 ns. The RMSD of LL channel seems to jump to 0.5 nm after 20 ns. A close look at Figure 3, we can see one LL molecule is exfoliated from the channel; meanwhile, the rest LL molecules in the membrane reserve the channel fairly well with a small RMSD (LL’ in Figure 2). Compared with the other three channels (FF, FL and LF), LL has smaller hydrophobic side chain moieties; therefore, LL and the membrane do not match completely, leading to the exfoliation of one LL molecule.

AV

FF

FL

LF

LL

Figure 3. Final snapshots of different channels in the lipid membrane. The phosphate atoms are represented by yellow spheres, water molecules within 1.2 nm of the channels are in red (atom O) and gray (atom H). The lipid heads and tails, as well as water molecules far from the channels, are omitted for clarity.

When a hydrophobic channel is embedded in a lipid membrane, thermodynamics requires that the channel length should match the membrane thickness. Otherwise, a hydrophobic mismatch may cause either tilting30 or aggregation31 of the channel. To examine the effect of mismatch, another FL channel was embedded in the lipid membrane (Figure 4a). The length of 7


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this FL channel is 5.3 nm, longer than the membrane thickness. Obviously, there is a mismatch between the FL channel and membrane. Consequently, the FL channel tilts to overcome the mismatch (Figure 4b), as also observed for shorter FL and LF channels in Figure 3. Additionally, several FL molecules are dissembled from the channel, which is scarcely seen in other types of water channels. Unlike simple tilting or aggregation, the non-covalently assembled dipeptide channel exhibits a new way (i.e. disassembly) to respond to hydrophobic mismatch. Nevertheless, the disassembly is irreversible and occurs when the channel length is longer than the membrane thickness. (a)

(b)

Figure 4. Mismatch of FL channel in the lipid membrane. The color scheme is same as Figure 1.

3.2. Water structure, dynamics and permeation Figure 5 illustrates the chain-like structure formed by water molecules in the four hydrophilic channels. Specifically, multiple water chains are observed in FF channel because of the large channel diameter (about 0.92 nm). Thus, water arrangement in FF channel is bit disordered. In FL channel with a diameter of 0.42 nm, water arrangement is more ordered than in FF channel. It is intriguing that FL channel is helical, and two chains of ordered water molecules are formed therein with a double helical structure. In LF channel with an elliptical channel, two 8


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water chains are formed; while a single water chain is observed in LL channel with a diameter of 0.32 nm.

FF

FL

LF

LL

Figure 5. Water structure in four hydrophilic dipeptide channels.

To further quantify water structure in the channels, hydrogen bonds (HB) were calculated on the basis of two geometrical criteria: (1) the distance between a donor and an acceptor ≤ 0.35 nm (2) the angle of hydrogen-donor−acceptor ≤ 30°.32 As listed in Table 2, each water in FF channel forms 1 HBWW and 0.9 HBWP. As a comparison, there exist 0.6 HBWW and 1.4 HBWP in FL channel. This suggests that water-dipeptide has a stronger interaction than water-water in FL channel. When the channel diameter decreases from FL to LF and LL channel, the HBWW tends to drop while the HBWP remains nearly the same. In LL channel, only 0.4 HBWW exists implying that water molecules in LL channel are largely segregated from one other.

Table 2. Numbers of water molecules, hydrogen bonds and permeate rates in the channels.a Dipeptide

NW

HBWW

HBWP

HBPP

P (ns-1)

FF

76.7 ± 7.1

1.0 ± 0.1

0.9 ± 0.1

0.9 ± 0.1

9.20 ± 0.46

FL

24.0 ± 1.7

0.6 ± 0.2

1.4 ± 0.1

0.8 ± 0.1

0.23 ± 0.15

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LF

21.4 ± 1.6

0.6 ± 0.2

1.3 ± 0.1

1.0 ± 0.1

0.10 ± 0.04

LL

14.5 ± 1.7

0.4 ± 0.2

1.5 ± 0.2

0.9 ± 0.2

< 0.02b

a. NW is the number of water molecules. HBWW and HBWP are the numbers of hydrogen bonds per water molecule for water-water and water-dipeptide, respectively. HBPP is the numbers of hydrogen bonds for dipeptide-dipeptide based on per dipeptide molecule. P: permeation rate (number of water molecules per ns). b. No water molecule was found to permeate through LL channel during 50 ns simulation, indicating the permeation rate is < 1/50 = 0.02/ns.

Water dynamics in the channels is quantified by the mean-squared displacement (MSD)

Ωi (t ) − Ωi (0)

2

, where Ω denotes the x, y or z coordinate. Form Figure 6, it is obvious that in

each channel, the MSD in the z direction contributes most to the total displacement. It indicates that the motion the z direction is more overwhelming than in x or y direction. Among the four channels, the MSD in FF channel is the largest. With decreasing channel diameter, the MSD drops. This is clearly seen by comparing the MSDs in FF and FL because the channel diameter decreases quite significantly from 0.92 to 0.42 nm. In LF and LL, the MSDs are close due to similar channel diameter. At a long time t, the MDS scales with t as MSD ~ t1/2, suggesting that water undergoes single-file diffusion in these narrow hydrophilic channels.

1

1

2

FL

0.1

MSD MSDx MSDy MSDz

0.01

1E-3

1

1

1

FF MSD(nm )

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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10

100

t (ps)

1000

LF

LL

0.1

0.1

0.1

0.01

0.01

0.01

1E-3

1

10

100

1000

0.001

1

10

100

t (ps)

t (ps)

1000

1E-3

1

10

100

1000

t (ps)

Figure 6. Mean-squared displacements in x, y, z directions for four dipeptide channels. The dashed lines indicate single-file diffusion.

Water permeation is examined in the four hydrophobic channels. The permeation event was 10


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counted when a water molecule entered into the channel from one end and exited from the opposite end.3,6,33 During calculation, the channel was represented by a cylinder with a diameter encircling all the dipeptides in the bilayer; moreover, the upper and lower ends of the cylinder were in accord with the average positions of phosphate atoms in the lipid bilayer. Water permeation is mainly governed by the channel diameter. In FF channel with the largest diameter among the four channels, the permeation rate is 9.20/ns (Table 2). This is higher than the rate in natural water channel aquaporin (3/ns),3 but lower than that in (6,6) carbon nanotube with a diameter of 4.7 Å (20/ns).6 The extremely fast rate in the carbon nanotube is due to its highly hydrophobic and smooth surface allowing water to move with minimal hindrance. Although the diameter of FL channel (0.42 nm) is a bit larger than aquaporin (0.32 nm), the rate in FL channel is one order lower than that in aquaporin due to its hydrophilic and rough surface. These results reveal the importance of hydrophobicity and smoothness of channel surface for fast water permeation. In LF and LL channels with the smallest diameter (0.35 and 0.32 nm), very slow rate is found (0.1/ns and < 0.02/ns, respectively).

5

5

5

FF Radii (Å)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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5

FL

LF

LL

4

4

4

4

3

3

3

3

2

2

2

-10 dyn/cm 0 dyn/cm 10 dyn/cm

2

1

20

30

z (Å)

40

50

1

30

40

50

1 25

30

35

40

z (Å)

z (Å)

45

1 25

30

35

40

45

50

55

z (Å)

Figure 7. Radii of FF, FL, LF and LL channels under the surface tensions of −10, 0, and 10 dyn/cm.

As mentioned earlier, the lipid membrane may undergo structure change upon lateral 11


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stress/strain, it is instructive to examine how the channel structure and water permeation are affected. Figure 7 shows the radii of FF, FL, LF and FF channels at three different surface tensions (−10, 0 and 10 dyn/cm), obtained by averaging over 100 snapshots. Under a negative surface tension, the lipid membrane is stressed and so is the embedded channel. Consequently, the channel radius tends to shrink. By contrast, the lipid membrane and the channel are strained under a positive surface tension, thus the channel radius expands to a certain extent. Different from rigid water channels like carbon nanotubes, water permeation in dipeptide channels exhibit a mechanistic response to surface tension. As shown in Figure 8 for FF, FL and LF channels, each channel shrinks under stress leading to a decline in water permeation. Nevertheless, the channel dilates under strain and a faster water permeation rate is seen. As the surface tension increases from −20 to 20 dyn/cm, the permeation rate changes from 6/ns to 10/ns in FF channel, 0.17/ns to 0.32/ns in FL channel, and 0.07/ns to 0.2/ns in LF channel. These changes correspond to 66.6%, 88.2% and 185.7% respective increase of permeation rate. This underlines the crucial role of surface tension in tuning water transport through the dipeptide channels. 0.5 -1

Permeation rate (ns )

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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10

FF

0.3

FL

LF

0.4 0.2

0.3

8

0.1

0.2

6 0.1 0.0

4

-40

-30

-20

-10

0

Tension (dyn/cm)

10

20

0.0

-20

-10

0

10

20

Tension (dyn/cm)

-20

-10

0

10

Tension (dyn/cm)

Figure 8. Water permeation rate versus surface tension in FF, FL and LF channels.

12


20

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4. Conclusion We have investigated the stability, water structure, dynamics and permeation in five dipeptide channels embedded in a DPPC lipid membrane. Only the hydrophilic channels (FF, FL, LF and LL) are found to be stable in the membrane, as attributed to the favorable interactions between the hydrophobic external surface of channels and the lipid tails. In addition to tilting, the channels can respond to hydrophobic mismatch by disassembling dipeptide molecules thus reducing channel length. Chain-like structure is formed by water in the channels, water arrangement is bit disorder in large FF channel but tends to be ordered in small channels. With increasing channel diameter, the hydrogen bonding of water becomes stronger and water mobility is faster. A single-file diffusion is observed for water in the hydrophilic channels. In FF channel, water permeation rate is estimated to be 9.20/ns, which is higher than natural water channel aquaporin (3/ns) but lower than in (6,6) carbon nanotube (20/ns). In LF and LL channels, the permeation rate is quite slow (0.1/ns and < 0.02/ns). The channel structure and water permeation exhibit a mechanistic response to stress/strain on the lipid membrane. Under stress, the channel diameter shrinks and permeation rate drops; in contrast, the channels diameter expands under strain and permeation rate rises. Thus, water transport through the dipeptide channels is governed by channel diameter, but can be subtly tuned by external stress/strain. This study suggests that dipeptide might be interesting as synthetic water channels.

Acknowledgments We

gratefully

acknowledge

the

A*star

of

Singapore

R-279-000-431-305) for financial support. 13


(R-279-000-475-305

and

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Reference (1)

Israelachvili, J. N. Soft and Biological Structures. In Intermolecular and Surface Forces (Third Edition); Academic Press: San Diego, 2011; pp 535-576.

(2) Sui, H.; Han, B. G.; Lee, J. K.; Walian, P.; Jap, B. K. Structural Basis of Water-Specific Transport through Aquaporin-1 Water Channel. Nature 2001, 414, 872-878. (3)

de Groot, B. L.; Grubmuller, H. Water Permeation across Biological Membranes: Mechanism and Dynamics of Aquaporin-1 and GlpF. Science 2001, 294, 2353-2357.

(4) Ketchem, R.; Hu, W.; Cross, T. High-Resolution Conformation of Gramicidin a in a Lipid Bilayer by Solid-State NMR. Science 1993, 261, 1457-1460. (5)

Barboiu, M.; Gilles, A. From Natural to Bioassisted and Biomimetic Artificial Water Channel Systems. Acc. Chem. Res. 2013, 46, 2814-2823.

(6) Hummer, G.; Rasaiah, J. C.; Noworyta, J. P. Water Conduction through the Hydrophobic Channel of a Carbon Nanotube. Nature 2001, 414, 188-190. (7) Okamoto, H.; Nakanishi, T.; Nagai, Y.; Kasahara, M.; Takeda, K. Variety of the Molecular Conformation in Peptide Nanorings and Nanotubes. J. Am. Chem. Soc. 2003, 125, 2756-2769. (8)

Hu, X.-B.; Chen, Z.; Tang, G.; Hou, J.-L.; Li, Z.-T. Single-Molecular Artificial Transmembrane Water Channels. J. Am. Chem. Soc. 2012, 134, 8384-8387.

(9) Görbitz, C. H. Microporous Organic Materials from Hydrophobic Dipeptides. Chem. Eur. J. 2007, 13, 1022-1031. (10) Afonso, R.; Mendes, A.; Gales, L. Peptide-Based Solids: Porosity and Zeolitic Behavior. J. Mater. Chem. 2012, 22, 1709-1723. (11)

Görbitz, C. H.; Gundersen, E. L-Valyl-L-Alanine. Acta Crystall. Sec. C 1996, 52, 1764-1767. 14


Page 15 of 17

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

(12)

Fletterick, R.; Tsai, C. C.; Hughes, R. E. Crystal and Molecular Structure of L-Alanyl-L-Alanine. J. Phys. Chem. 1971, 75, 918-922.

(13) Görbitz, C. H. An Exceptionally Stable Peptide Nanotube System with Flexible Pores. Acta Crystall. Sec. B 2002, 58, 849-854. (14)

Henrik Gorbitz, C. Nanotubes from Hydrophobic Dipeptides: Pore Size Regulation through Side Chain Substitution. New J. Chem. 2003, 27, 1789-1793.

(15) Görbitz, C. H. Nanotube Formation by Hydrophobic Dipeptides. Chem. Eur. J. 2001, 7, 5153-5159. (16)

Soldatov, D. V.; Moudrakovski, I. L.; Ripmeester, J. A. Dipeptides as Microporous Materials. Angew. Chem. Int. Ed. 2004, 43, 6308-6311.

(17)

Comotti, A.; Bracco, S.; Distefano, G.; Sozzani, P. Methane, Carbon Dioxide and Hydrogen Storage in Nanoporous Dipeptide-Based Materials. Chem. Commun. 2009, 284-286.

(18) Afonso, R. V.; Durao, J.; Mendes, A.; Damas, A. M.; Gales, L. Dipeptide Crystals as Excellent Permselective Materials: Sequential Exclusion of Argon, Nitrogen, and Oxygen. Angew. Chem. Int. Ed. 2010, 49, 3034-3036. (19) Pan, Y.; Birkedal, H.; Pattison, P.; Brown, D.; Chapuis, G. Molecular Dynamics Study of Tryptophylglycine: A Dipeptide Nanotube with Confined Water. J. Phys. Chem. B 2004, 108, 6458-6466. (20) Kaucher, M. S.; Peterca, M.; Dulcey, A. E.; Kim, A. J.; Vinogradov, S. A.; Hammer, D. A.; Heiney, P. A.; Percec, V. Selective Transport of Water Mediated by Porous Dendritic Dipeptides. J. Am. Chem. Soc. 2007, 129, 11698-11699. (21) Smart, O. S.; Goodfellow, J. M.; Wallace, B. A. The Pore Dimensions of Gramicidin-A. Biophys J 1993, 65, 2455-2460. (22) Jorgensen, W. L.; Maxwell, D. S.; Tirado-Rives, J. Development and Testing of the OPLS All-Atom Force Field on Conformational Energetics and Properties of Organic Liquids. J. Am. Chem. Soc. 1996, 118, 11225-11236. 15


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(23)

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Tieleman, D. P.; Maccallum, J. L.; Ash, W. L.; Kandt, C.; Xu, Z.; Monticelli, L. Membrane Protein Simulations with a United-Atom Lipid and All-Atom Protein Model: Lipid-Protein Interactions, Side Chain Transfer Free Energies and Model Proteins. J. Phys. Condens. Matter 2006, 18, S1221-1234.

(24)

Jorgensen, W. L.; Chandrasekhar, J.; Madura, J. D.; Impey, R. W.; Klein, M. L. Comparison of Simple Potential Functions for Simulating Liquid Water. J. Chem. Phys. 1983, 79, 926-935.

(25) Cheng, A. L.; Merz, K. M. Application of the Nose-Hoover Chain Algorithm to the Study of Protein Dynamics. J. Phys. Chem. 1996, 100, 1927-1937. (26)

Andersen, H. C. Molecular Dynamics Simulations at Constant Pressure and/or Temperature. J. Chem. Phys. 1980, 72, 2384-2393.

(27) Bennun, S. V.; Dickey, A. N.; Xing, C.; Faller, R. Simulations of Biomembranes and Water: Important Technical Aspects. Fluid phase equilibria 2007, 261, 18-25. (28) Essmann, U.; Perera, L.; Berkowitz, M. L.; Darden, T.; Lee, H.; Pedersen, L. G. A Smooth Particle Mesh Ewald Method. J. Chem. Phys. 1995, 103, 8577-8593. (29) Berendsen, H. J. C.; Spoel, D. v. d.; Drunen, R. v. Gromacs: A Message-Passing Parallel Molecular Dynamics Implementation. Comp. Phys. Comm. 1995, 91, 43-56. (30)

Lopez, C. F.; Nielsen, S. O.; Moore, P. B.; Klein, M. L. Understanding Nature's Design for a Nanosyringe. Proc. Natl. Acad. Sci. (USA) 2004, 101, 4431-4434.

(31)

Parton, Daniel L.; Klingelhoefer, Jochen W.; Sansom, Mark S. Aggregation of Model Membrane Proteins, Modulated by Hydrophobic Mismatch, Membrane Curvature, and Protein Class. Biophys. J. 2011, 101, 691-699.

(32)

Luzar, A.; Chandler, D. Hydrogen-Bond Kinetic in Liquid Water. Nature 1996, 379, 55-57.

(33)

Lu, D. Accelerating Water Transport through a Charged Swcnt: A Molecular Dynamics Simulation. Phys. Chem. Chem. Phys. 2013, 15, 14447-14457.

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Abstract Entry

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Dipeptides Embedded in a Lipid Bilayer Membrane as Synthetic Water

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