Molecular mechanics modeling of the adsorption of methionine on graphite

Surface Science 604 (2010) 2084–2090

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Surface Science j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / s u s c

Molecular mechanics modeling of the adsorption of methionine on graphite Andreas Riemann ⁎, Brandon E. Owens Department of Physics and Astronomy, Advanced Materials Science & Engineering Center, Western Washington University, Bellingham, WA 98225, United States

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Article history: Received 20 May 2010 Accepted 19 August 2010 Available online 8 September 2010 Keywords: Semi-empirical models and model calculations Physical adsorption Self-assembly Graphite

a b s t r a c t In this study we were modeling the adsorption of the amino acid methionine on a graphite surface using molecular mechanics calculations. We were employing two different force fields, namely MM+ and AMBER, and considering the molecule in its non-ionic and zwitterionic form. The surface was modeled as a single sheet of graphite. We found that each of the force fields delivers qualitative consistency with experimental results, but the AMBER force field with the parameter set of AMBER3 leads to the best quantitative agreement regarding adsorption energy, bonding energies and distances. © 2010 Elsevier B.V. All rights reserved.

1. Introduction Molecular self-assembly plays a crucial role in biology and is the focus of many research projects in the field of nanotechnology. Here, the goal is to create structures which could be used for further applications in molecular electronics, biosensors, or medical applications. The control of these nanostructures is a fundamental challenge in surface science. Especially interesting are so-called molecular wires, one-dimensional arrangement of molecules which are preferably selfassembled. There is a wide variety of molecules to choose from, natural occurring species as well as specifically engineered molecules. Methionine molecules play a significant role in the metabolism of homocysteine in the human body [1–6]. This process is important in the cardiovascular system. Especially the interaction of different amino acids like methionine, homocysteine, cysteine and lysine, are at the root of different cardiovascular diseases due to protein reactivity [7–10]. Therefore, the present system is not only interesting with respect to the interaction between amino acids and surfaces but also relevant for the medical community. In a previous experimental study, we have shown how the amino acid L-methionine can be used to create regularly spaced molecular wires under ambient conditions as well as under Ultra-High Vacuum (UHV) conditions [11,12]. By means of self-assembly, the amino acid arranges itself into an array of well-ordered stripes of uniform width and separation. The spacing of these wires can be controlled with the deposition amount of the amino acid, whereas the width stays constant. The regular separation of individual wires suggests a long-

⁎ Corresponding author. Tel.: +1 360 650 2856. E-mail address: [email protected] (A. Riemann). 0039-6028/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.susc.2010.08.023

range interaction among them, probably caused by the side chain of this amino acid. The system of methionine on graphite is the focus of this modeling study. For experimental researchers, it has become common practice to complement their data with computational/modeling data. Especially the expanded use of experimental methods like Scanning Tunneling Microscopy (STM) or Atomic Force Microscopy (AFM) where the position of individual molecules and their electronic state can be imaged have led to a demand of easy accessible modeling capability [13,14]. Ideally, one would use powerful and versatile methods like Density Functional Theory (DFT), but this method is not always accessible to experimental researchers and is often computationally very expensive for the system of interest. The availability of modeling software, like Hypercube's HyperChem® Molecular Modeling software package made it possible to run these kind of simulations from desktop computers without the need of an expensive computer cluster and modeling software. The present calculations are evaluated regarding their agreement with previous results with respect to energies and geometries found for the adsorption of amino acids on graphite surfaces. The experimental results of methionine rows on graphite can be seen in Fig. 1, discussed extensively in a previous publication [11]. We found that methionine forms rows of dimers with a width of about 18 Å. The width of the wire is determined by two methionine molecules arranged with their carboxyl and amino group facing each other. Along the direction of the methionine rows it was found that the distance between neighboring molecules is equivalent to twice the distance of equivalent points on the graphite surface measuring about 8.6 Å. Classical molecular mechanics calculations employing a variety of force field parameters are used to supplement experimental findings. These force fields come with diverse parameter sets enabling wide use

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~4

5Å

Fig. 3. Geometry of methionine in non-ionic form adsorbed on the graphite surface. The inertial axis along the side chain of the molecule is nearly perpendicular to the surface indicating a flat adsorption geometry of the molecule on the surface as observed in the experimental data.

~1

8Å

50Å Fig. 1. STM image of methionine on graphite surface. At coverage of about 40% a row spacing of 45 Å can be observed. The width of the rows (~ 18 Å) is determined by the length of two methionine molecules facing each other. Inset shows individual methionine molecules imaged as elliptical features [11].

in computational chemistry and the medical research community as well [15,16]. The applicability on our system will be tested and discussed in this study. 2. Methods and materials For the adsorption of methionine on graphite we carried out molecular mechanics calculations [17] with the software package HyperChem 7.5 [18]. We used 3 different force field parameter sets to compare the results of methionine adsorption on a graphite surface. Each of these force fields can be described by the following general expression: ∑

E=

E+

bond stretching

+

∑ non bonded

E+

∑

E+

bond bending

∑ E+ dihedral

∑

E

out of plane

∑ E Coulomb

with different parameters for each force field [19]. The choices of force fields were the universal MM+ force field as well as the AMBER (Assisted Model Building with Energy Refinement) force field with two different parameter sets (AMBER3 and AMBER94) which was developed especially suitable for amino acids. The MM+ force field is

a

built on an extension of MM2, a force field established by N.L. Allinger in 1977 [20] and expanded multiple times since then [21,22]. It is a force field which can be applied to many situations but lacks the accuracy of force fields aimed at specific cases. AMBER, the second force field used, was introduced by P. Kollman's group and is mostly used for nucleic acids and proteins, thus very applicable to the present case of amino acids [23–26]. The main differences of the three used force field parameter sets are: MM+ has higher than quadratic terms for the bond energies and the angle calculations. Furthermore, for the Coulomb interaction it uses dipoles instead of point charges. The non-bonding van-der-Waals term has exponential form. On the other hand, AMBER3 has explicit hydrogen bonding terms in 10–12 form, and AMBER94 includes the contribution of hydrogen bonds in its van-der-Waals energy term [18]. For the optimization of the individual molecules all forces described in the equation above are employed to find the energetically best configuration. Since the self-assembly of methionine molecules does not lead to chemical bonding between two molecules, the optimization of the adsorption geometry is only governed by the non-bonding forces included in the last two terms. These involve vander-Waals repulsive forces at close range, Lennard-Jones long-range attractive interactions, electrostatic Coulomb forces and hydrogen bonding terms. We chose the system of the amino acid methionine on a graphite surface to extend the scope of our previous work [11]. Additionally, there are other experimental results for this amino acid [12] and other similar amino acids [27] available for comparison. The graphite substrate was simulated as a single layer of graphene with a lattice constant of 1.4 Å (see Fig. 2). This single layer takes the electronic structure of graphene into account but does not account for potential image charges or screening effects observed in experiments with the graphite sample. The template has a dimension of 60 Å × 60 Å. This size

b

C

S

O

c

N

H

Fig. 2. Methionine in its non-ionic form (a) and zwitterionic form (b). The substrate used for the calculations is a single sheet of graphite with a lattice constant of 1.4 Å (c).

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In order to allow more general comparisons of the adsorption under different conditions (temperature, solvent etc.) and with previous calculations [29] as well as limit the parameter space, all calculations were performed in vacuo and at a temperature of zero K. The calculations carried out in this study yield a comparison of the total energy of the methionine molecules and the surface for different configurations. In a first step the graphite surface was constructed with the atomic structure and C–C bond length according to bulk graphite as seen in Fig. 2c. The methionine molecules were geometryoptimized using the respective force field parameters for these calculations. The adsorption energy was determined and evaluated. For the subsequent calculations, this first methionine molecule was fixed with its center of mass at the origin of our coordinate system. Then a second optimized molecule was positioned on a 20 Å × 20 Å grid with a step width of 0.1 Å around the origin and the energies of each of these configurations was recorded. This second molecule was oriented in two different configurations extracted from experimental results, namely parallel to the stationary molecule and anti-parallel to

Table 1 Table for adsorption energies of one methionine molecule on graphite surface using different force fields. Molecular configuration

Adsorption energy [eV]

Non-ionic Zwitterionic

AMBER3

AMBER94

MM+

0.39 0.44

0.69 0.81

0.74 0.65

guarantees that there are no significant boundary effects observed for the adsorption of methionine around the center of the template. The methionine molecule was modeled in its non-ionic state and in its zwitterionic state. Although amino acids are not found in their zwitterionic state from gas phase [28], previous experiments have shown that methionine during the adsorption on surfaces can be found in its zwitterionic state [12]. Both configurations of methionine are depicted in Fig. 2.

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Fig. 4. Total energy maps of methionine on graphite in anti-parallel configuration for methionine in non-ionic form (a, c, and e) and in zwitterionic form (b, d, and f) using the different force field parameter sets AMBER3 (a and b), AMBER94 (c and d) and MM+ (e and f). The points of lowest energies can be found in the red regions.

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it. These two configurations simulate the width of the dimer rows (anti-parallel) and orientation along the dimer rows (parallel).

0.00

3. Results and discussion

5

The simulations were compared to previous calculations as well as experimental results with the following points chosen for comparison and validation:

-0.05

-0.10 0 -0.15

• Adsorption geometry and adsorption energy of a single molecule on the graphite surface. • Dimer construction of molecules as found in previous experimental results [11]. • Hydrogen bond length and energies of facing amino and carboxyl groups for anti-parallel configuration. • Parallel orientation of molecules including spacing and binding energy. The first evaluation of our simulations was concerning the adsorption geometry and adsorption energy of a single molecule on the graphite surface. All calculations show that the methionine molecules are lying flat on the surface. The energetically most favorable situations are attained when the amino and carboxyl groups as well as the sulphur in the side chain are close to the graphite surface. This is consistent with our previous results of adsorption of methionine on graphite. The same behavior was found for other amino acids on surfaces [12,27,30]. Fig. 3 shows an example of the adsorption geometry of a non-ionic methionine molecule on the graphite surface. Clearly, one of the inertial axes of the molecule is nearly parallel with the surface. This axis represents the long axis of the elliptical features as which methionine is imaged by using STM (see inset in Fig. 1). To find the adsorption energy for a single methionine molecule, we compared the energy of an isolated molecule in free space with the energy for the molecule on the surface. The data are summarized in Table 1. The values obtained are all comparable to previous calculations for amino acids on graphite [29]. There it was found that the adsorption energy is around 0.5 eV consistent with our calculations. The force field AMBER94 yields the highest adsorption energy for the single methionine molecule. For both of the AMBER force field parameter sets the zwitterionic form yield a slightly higher adsorption energy attributed to the polar nature of this molecule which can lead to lower total energy when brought close to a surface. In order to evaluate the arrangement of two methionine molecules facing each other with their carboxyl and amino group (in dimer configuration) we calculated the energy of two methionine molecules on the graphite surface in anti-parallel arrangement. One molecule was kept stationary whereas the second molecule was rotated by 180° in the adsorption plane and moved around in a 20 Å × 20 Å grid. For each point (a total of 40,000 positions per force field and molecule configuration) an energy value was obtained. These values can be plotted in surface plots as seen in the energy maps in Fig. 4. The first molecule is fixed with its center of mass at the origin of the map and the second molecule is positioned according to the x- and ycoordinates of the graph. Clearly, when the molecules are overlapping or are very close, the total energy values are very high due to strong repulsive forces (purple region of graphs). The lowest energies can be found at the red regions, which were used to infer the molecular configurations seen in Fig. 5. Previous experiments show that methionine molecules are preferably arranged in dimer rows with the carboxyl and amino groups facing each other. The bonding of the molecules is accomplished through hydrogen bonds between the amino group and the carboxyl group. These bonds enable stable dimer rows as observed in the experiments [12]. The simulations with different force fields show that this configuration is indeed an energy minimum as indicated by the red regions in the energy maps in Fig. 4. From these energy maps we are able to infer the configuration of two methionine molecule

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a

b

c

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Fig. 5. Top panel: Example of energy map with the two methionine molecules positioned at an energy minimum configuration in anti-parallel configuration. Bottom Panel: Anti-parallel configuration of methionine dimers with methionine in non-ionic form (a, c, and e) and in zwitterionic form (b, d, and f) using the different force field parameter sets AMBER3 (a and b), AMBER94 (c and d) and MM+ (e and f) as deduced from the energy maps in Fig. 4.

facing each other. The results of deduced configurations for methionine molecules in anti-parallel arrangement can be seen in Fig. 5. For all six modeling runs a configuration with the carboxyl group of one molecule close to the amino group of the other molecule was obtained as energy minimum. Furthermore, the inferred geometry of slightly offset molecules in the model is comparable to the STM image of the experimental results (see inset of Fig. 1). All configurations result in a dimer length of about 18 Å in excellent agreement with the experimentally determined value. Another feature extracted from these energy maps are inter-molecular binding energies. These values were found by comparing the energies for two methionine molecules adsorbed on a graphite surface not interacting with each other with the energies found for optimal configuration. In Table 2 the binding energies obtained from the energy maps as well as Table 2 Table for hydrogen bond length between carboxylic oxygen and amino hydrogen and binding energies of two methionine molecules in anti-parallel configuration. Molecules

Non-ionic Zwitterionic

Bond length [Å]

Binding energies [eV]

AMBER3

AMBER 94

MM+

AMBER3

AMBER 94

MM+

2.5 2.0

3.2 2.3

3.2 2.9

0.10 0.04

0.09 0.03

0.06 0.04

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configuration of the molecules can lead to a stretching of these bonds and subsequently to a distortion in the energy values [35,36]. The next step was to simulate the configuration of two methionine molecules in parallel orientation. Here, in our simulation the second molecule is kept in the same orientation as the first, stationary molecule. This second molecule was again moved on a 20 Å × 20 Å grid in 0.1 Å steps, and the energy values for each point were calculated. The data for these calculations are summarized as energy maps in Fig. 6. The lowest energies can be found in symmetric positions with respect to the origin as can be expected for the parallel configuration. The energetically most favorable position was used as the adsorption position of the second methionine with respect to the stationary molecule at the origin of the energy map. These calculations lead to data of binding energies along this direction again by comparing two independent methionine molecules on graphite with two molecules in their energetically most favorable position. The data for the spacing of the two molecules and the binding energies are summarized in Table 3.

the bond lengths of hydrogen bonds between amino and carboxyl groups from the models in the bottom panel of Fig. 5 are summarized. Our calculations yield bond lengths between 2.0 Å and 3.2 Å and binding energies between 0.03 eV and 0.1 eV. Hydrogen bond energies vary depending on the situation of the involved atoms. Typical bond energies for carboxylic oxygen and amino hydrogen are about 0.08 eV per bond [31]. Our results agree with this value taking into account that force fields have been shown to slightly underestimate the hydrogen bond energies [32]. Hydrogen bond lengths between an amino group and a carboxyl group have been found to be around 2 Å using ab initio energy calculations [33]. Regarding bond length, AMBER3, with explicit hydrogen bond terms, yields the best comparison with these previous results lying within an error of 10% observed for other calculations comparing force fields and DFT methods [34]. However, one has to be careful when comparing hydrogen bond length and associated energies during adsorption on surfaces with hydrogen bonds in solution, since a commensurate

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Fig. 6. Total energy maps of methionine on graphite in parallel configuration for methionine in non-ionic form (a, c, and e) and in zwitterionic form (b, d, and f) using the different force field parameter sets AMBER3 (a and b), AMBER94 (c and d) and MM+ (e and f). The points of lowest energies can be found in the red regions.

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Table 3 Table for binding energies and spacing of two methionine molecules in parallel configuration.

0.00

Molecules

Non-ionic Zwitterionic

Spacing [Å]

Binding energies [eV]

AMBER3

AMBER 94

MM+

AMBER3

AMBER 94

MM+

5.8 6.1

6.4 5.9

6.5 6.2

0.10 0.04

0.07 0.08

0.09 0.10

5 -0.05

0

Previous experimental results show that methionine rows are along the perpendicular direction to the individual molecule's inertial axis (seen in STM images as the long axis of the oval shaped molecules). Our calculations lead to a model in which this configuration can be obtained by subsequent addition of molecules in equivalent positions of the parallel energetically most favorable situation. This setup leads to rows which mimic the experimental findings (see Fig. 7). The overall geometry in this direction found with the simulations is in excellent agreement with the experiments. The interaction of methionine molecules in parallel configuration is accomplished through hydrogen bonds of the carboxyl and amino group with each other and with the side chain of the methionine molecules. This bonding is comparable in its energies to the values obtained for the anti-parallel configuration. The spacing of methionine molecules within the rows was experimentally determined to be about 8.4 Å on the graphite surface [11]. For experiments on a different substrate like Ag(111) this spacing was measured to be only 5.4 Å [12]. Comparing these two experimental findings show that the spacing between two molecules is determined by the inter-molecular hydrogen bonds as well as the bonding configuration with the substrate and any commensurability which arises from it. In our calculations we obtain a spacing of about 6 Å, a value between the 5.4 Å found for a silver surface and 8.4 Å for a graphite surface. The quantitative discrepancy of the simulation of methionine on graphite for the distance between molecules can be attributed to the interactions of the molecules with the graphite surface. Although the surface has clearly an influence on the energy for the methionine adsorption, as evident by the periodic structure seen in the energy maps (Figs. 4 and 6) at the outer limits, the full effect of it is not included in these simulations.

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4. Summary The use of molecular mechanics calculations enabled us to model the adsorption of methionine on a graphite surface using three different force field parameter sets with the molecule in its non-ionic and zwitterionic form. All six configurations lead to excellent qualitative agreements with the experimental results found before. Nevertheless, the use of the AMBER force field with the AMBER3 parameter set and methionine in its zwitterionic form has given the best quantitative agreement regarding dimer formation (offset molecules with hydrogen bond length of 2.0 Å). Since this parameter set uses explicit energy terms for hydrogen bonds, this result is not surprising. For this force field an additional calculation was performed. Here, the starting configuration consisted of a methionine dimer in the configuration seen in the bottom panel b) of Fig. 5. A third methionine molecule was moved in parallel configuration on a 20 Å × 20 Å grid. The resulting total energy map with resulting molecular configuration can be seen in Fig. 8. The hydrogen bonds between the anti-parallel and parallel molecules are indicated. The spacing between molecules was determined to be 6.7 Å somewhat higher than for the parallel configuration without an anti-parallel methionine molecule (see Table 3). The molecular configuration obtained using the AMBER3 parameter set leads to the best agreement with the experimental results. This study has shown that molecular mechanics calculations can be a useful tool for the experimental researcher when complementing

Fig. 7. Top panel: Example of energy map with the two methionine molecules positioned at their lowest energy configuration in parallel configuration. Bottom panel: Parallel configuration of methionine molecules which leads to rows as observed in experiments. Methionine was modeled in non-ionic form (a, c, and e) and in zwitterionic form (b, d, and f) using the different force field parameter sets AMBER3 (a and b), AMBER94 (c and d) and MM+ (e and f) for the respective configurations.

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[1] [2] [3] [4] [5] [6] [7]

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[8] [9] [10] [11] [12] [13] [14] [15]

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Fig. 8. Energy map with the three zwitterionic methionine molecules positioned at their lowest energy configuration in parallel and anti-parallel configuration calculated using the AMBER3 force field parameter set. Indicated are the hydrogen bonds between the amino group and the carboxyl group of the zwitterionic methionine.

[16] [17] [18] [19] [20] [21]

experimental results with simulation data. However, one has to be careful when using “black box” approaches for complex systems [37]. The appropriate force field for the situation modeled needs to be chosen in order to get useful results. In our case the force field AMBER specifically designed for nucleic acids and proteins with the parameter set of AMBER3 which includes an explicit energy term for hydrogen bonds turned out to yield the best similarities with the experimental results. Nevertheless, in future investigations, we would like to extend and improve this modeling approach to a more realistic surface of a hydrogen-terminated graphite sheet and/or to a double layer of graphite with a buckled structure to mimic experimental conditions closer.

Acknowledgements We would like to thank the Chemistry department at Western Washington University for the use of the modeling software.

[22] [23] [24] [25] [26] [27] [28] [29] [30] [31] [32] [33] [34] [35] [36] [37]

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