1284
J. Phys. Chem. C 2007, 111, 1284-1290
Adsorption of Leucine-Rich Amelogenin Protein on Hydroxyapatite (001) Surface through -COO- Claws Xin Chen, Qi Wang, Jiawei Shen, Haihua Pan, and Tao Wu* Department of Chemistry, Zhejiang UniVersity, Hangzhou 310027, People’s Republic of China ReceiVed: July 22, 2006; In Final Form: NoVember 8, 2006
Amelogenin is the main component of the organic matrix necessary to the formation of tooth enamel by directing the hydroxyapatite (HAP) growth. However, the detailed mechanism of adsorption between amelogenin and HAP is still not clear. In this report, simulations of the dynamic behavior of six different orientations of leucine-rich amelogenin protein (LRAP), the amelogenin splice variant, on a fixed hydrophilic HAP surface (001) were performed. Energy minimization, molecular dynamics (MD), and steered molecular dynamics (SMD) simulations were integrated in carrying this study. The results are highly consistent with the previous experimental findings. It was confirmed that the carboxyl groups contributed mainly to the adsorption of LRAP on the HAP (001) surface. Moreover, it was found that the -COO- claw of LRAP grasps the calcium ion with its two oxygen atoms in a special triangle form. This interaction form can resist external forces and is the key factor of the adsorption between LRAP and HAP.
Introduction The interaction of protein molecules with inorganic materials is one of the most interesting research topics in many fields, such as biomineralization, nanomaterials, biochemistry, and industry.1-4 Understanding the noncovalent bonding of a protein to an inorganic surface at the atomic level plays a very important role in the development of new biomaterials, especially for biocompatible medical implants. As we know, hydroxyapatite [HAP, Ca10(PO4)6(OH)2] is one of the main inorganic components of mammalian bone and teeth, and it also serves as an ideal model for studies in these fields. Because of its good biological compatibility, HAP is a promising novel hard tissue implant material. Studies show that enamel is composed of long and highly oriented needle-like HAP crystals.5-8 Recently, experiments also demonstrated that the growth process of HAP is controlled by the interactions between the organic matrix and the HAP crystal.9-13 These interactions are the key factors that could graduate the nucleation and development of HAP crystals. Among all of the proteins present in enamel matrix and interacting with the HAP, amelogenin and albumin attracted much attention recently. Many experimental techniques have been developed and applied to study the important interactions between the amelogenin and the HAP. For example, solid-state NMR (ssNMR) and atomic force microscopy (AFM) were extensively used to explore their structure features.14-16 The AFM analysis illustrated that the adsorption strength of amelogenin is much greater than that of albumin, and this adsorption difference may be caused by protein structure characteristics.17-19 The charge distribution of protein was reported to be essential to the interactions of protein with inorganic crystals; in particular, the carboxyl groups of the protein is the primary factor affecting the growth of HAP.20-22 The ssNMR studies revealed that the -COO- terminus of amelogenin is one of the closest groups to the surface of HAP.5 Once the charged -COO- terminus was cut off, the affinity of LRAP to the HAP * Corresponding author. Fax: +86-571-87951895. E-mail: tao_wu@zju. edu.cn.
was sharply decreased.23 All of these experiments indicated that the -COO- terminus was the primary adsorption group. These results have already extended our understanding of the dynamic behavior of amelogenin on HAP surface greatly. However, the experimental results could not provide us enough microscopic details about how the protein interacts with the HAP crystal, and the interaction mechanism is still not clear. After two decades of development, the molecular simulations have already been proven to be of great importance in understanding the absorption of proteins at the atomic level.24-27 It can provide detailed information about the structure changes and the sites of effective adsorption groups. The adsorption and desorption characteristics can be explicitly illustrated by the steered molecular dynamics (SMD). In SMD simulation, an external force is applied to the molecule of a simulation system to probe their mechanical properties.28-30 In this work, we presented the molecular dynamics (MD) and SMD simulations on the dynamic behavior of amelogenin on the HAP surface. The system we investigated is composed of leucine-rich amelogenin protein (LRAP), HAP crystal, and water molecules. LRAP is an amelogenin splice variant and contains the charged -COO- terminus of the amelogenin,5,18 and the HAP (001) surface was selected in the simulations. It is one of the most extensively studied surfaces of HAP both experimentally and computationally.31-33 As suggested by many experiments, HAP is prone to elongate in the direction of the c-axis during its growth.10,34,35 Thus, in this work, both MD and SMD simulations were conducted to study the interactions of LRAP with the HAP (001) surface in the c-axis direction. Adsorption and desorption behaviors of LRAP were investigated to demonstrate the mechanism of graduating and elongating HAP at the atomic resolution. Methodology The amino-acid sequence of LRAP, which contains 59 residues, was derived from the experimental work.5 Because LRAP is an amelogenin splice variant and its tertiary structure has not been determined, the secondary structure prediction by
10.1021/jp0646630 CCC: $37.00 © 2007 American Chemical Society Published on Web 12/23/2006
Adsorption of LRAP on Hydroxyapatite (001) Surface
J. Phys. Chem. C, Vol. 111, No. 3, 2007 1285
self-optimized prediction method with alignment (SOPMA)36 was carried out on the Network Protein Sequence Analysis (NPS@) server.37 The tertiary structure was then roughly built in HyperChem v7.5 according to the predicted secondary structure. As the coarse structure of LRAP was obtained, LRAP was immersed in a water box with a size of 51 × 54 × 57 Å3, and then energy minimization and 2 ns MD simulation were conducted with NAMD.38 In the MD simulation, the root-meansquare deviation (rmsd) of all residues and the total energy of LRAP fluctuated around a constant value. Thus, we presumed that a stable tertiary structure was achieved. Because the module of LRAP may be roughly described in a rectangular box, we selected six different starting orientations, corresponding to each face of the protein box lying on the HAP (001) surface in the c-axis. Both the HAP and the LRAP molecules were then immersed in a periodic SPC model39 water box, and the box volume was set to 56.6 × 65.4 × 100.1 Å3. The simulations were performed with NAMD using Charmm27 All-Atoms (AA) force field40 with hydroxyapatite parameters supplemented. The original module of HAP (P63/m) was extracted from the American Mineralogist Crystal structure database.41 The parameters of force field for HAP were taken from the research work of Hauptmann et al.42 This force field has been proven to describe the structure and the nature of HAP at different temperatures correctly. The unit cell parameters obtained from the simulation were in approximate agreement with that of the observation with a relative error less than 1%. The parameters for the cross interactions were obtained from the LorentzBerthelot mixing rule.43
σij )
(σii + σjj) 2
ij ) xiijj
(1) (2)
For the simulations in the biomaterial fields, this mixing rule was extensively used to calculate the intermolecular potential between pairs of non-identical atoms.44-46 A time step of 2 fs was used with atom coordinates saved every 1 ps. Particle Mesh Ewald (PME) summation was used to calculate the full-system periodic electrostatic interactions, with a cutoff distance of 12 Å for the separation of the direct and reciprocal space summation. The van der Waals interactions were truncated at 13.5 Å. During the MD runs, the Langevin method was employed to control the constant temperature at 310 K and the pressure at 101.3 kPa. Energy minimization was performed to optimize the geometry of LRAP, and then the MD simulation was applied to equilibrate the system for 1 ns. A series of SMD simulations were conducted following the MD simulation. On principle, SMD is carried out by attaching a harmonic restraint to one or more atoms in the system, and then varying either the stiffness of the restraint or the position of the restraint to pull the atoms along. Constant velocity pulling (PCV) is one of the basic methods of SMD. In the PCV simulation, the SMD atom is attached to a dummy atom via a virtual spring.28 This dummy atom moved at constant velocity, and then the force between them is measured using:
B F ) -∇U
(3)
1 r -b r 0)‚n b] 2 U ) k[Vt - (b 2
(4)
where ∇U is the potential energy, k is the spring constant, V stands for pulling velocity, t is the time, b n is the direction of
pulling, and b r and b r0 are the instantaneous position and the initial position of the SMD atom, respectively. In this work, HAP crystal was fixed and the external force was applied to LRAP to pull the protein molecule at a constant velocity in the direction of the c-axis. The interaction between LRAP and HAP is very complicated, and there are many factors that contribute to it. Actually, it is out of the capability of current simulation techniques to take all of these factors into account simultaneously. To keep on the safe side and to avoid the complicated correlative factors from misleading our understanding of these phenomena, one has to change these variables step by step. In other words, a perturbation simulation should be performed in a controlled way. To obtain usable information from these SMD simulations, an observation window should be selected carefully. The spring constant should be weak enough to enhance the sensitivity of changes and strong enough to make LRAP follow the external force. If the pulling velocity were adjusted too fast, it would lose information regarding the relaxation of the protein. On the other hand, if it was too slow, it is hard to avoid the surrounding noise of water molecules. One reason is that LRAP, as the major component of functional segments of amelogenin, has a quite loose and soft structure. To obtain this observation window in this work, a series of simulations on varied parameters were performed, and the results were checked carefully to get converged results. In the end, the spring constant k was set to be 30 kcal mol-1 Å-2, and the pulling velocity was fixed at 5 × 10-4 Å fs-1 to obtain good SMD observation window. The details of SMD parameters selection were provided in the Supporting Information. The pulling distance was set to be 20 Å according to the system size and the periodic boundary conditions. 1000 frames of trajectories were deposited during the SMD simulation. We would like to point out that if this technique was performed to other systems, the converged parameters may be different and should be checked. The adsorption mechanism of LRAP on the HAP (001) surface will then be analyzed by the combination of the force-time curves and the trajectory animation. Results and Discussion (1) MD Simulations. The starting orientation of LRAP was divided into six cases. The first one, denoted as A, is the initial face of LRAP, and the other five faces were obtained through turning the protein box around the x- and y-axes, denoted as B, C, D, E, and F. They were rotated clockwise 180° around the x-axis, 270° around the y-axis, 90° around the x-axis, 270° around the x-axis, and 90° around the y-axis, respectively. The MD simulation is essential to achieving equilibrium state, and generally there are two criterions to judge whether it achieves equilibrium or not, that is, the potential energy of LRAP and the radius of gyration during the simulation. LRAP was immersed in a complex system with HAP and water molecules. To describe the final state of LRAP more exactly, the potential energy of LRAP was extracted individually from the simulation system. The potential energy is illustrated in Figure 1, and the radius of gyration is also presented in Figure 2. Both criterions indicate that all six cases reached equilibrium states ahead of the SMD simulations. (2) SMD Simulations. After 1 ns MD simulation, without any disturbances applied to LRAP and HAP, an equilibrium state was relegated to the SMD simulations as the starting state. During the SMD simulation, all atoms of the HAP crystal were fixed, and an external force was applied to every atom of LRAP uniformly to keep LRAP moving at a constant velocity. As to
1286 J. Phys. Chem. C, Vol. 111, No. 3, 2007
Chen et al.
Figure 2. Radius of gyration of LRAP backbone versus simulation time for all six cases. The radius of gyration changed with small fluctuation, which indicates that all six cases reached the stable states.
Figure 3. Pulling forces with respect to SMD time for the six cases. The peaks show the formation and breaking of both inter- and intramolecular interactions, for example, H-bonds. The notable peaks in these two figures are consistent with the interaction variations observed from the trajectories.
Figure 1. Potential energy changes of LRAP with respect to simulation time. All of the potential energies of LRAP changed mildly and fluctuated in a narrow range during 1 ns MD simulation, which indicates that the systems have achieved the equilibrium states.24,25
water molecules, they all moved freely within periodic system boundary. The force changes with respect to time were recorded through the PCV simulation. The adsorption cases could be explored by the changes of pulling force, as shown in Figure 3. The LRAP was placed closely onto the HAP surface and the pulling forces applied to it started from zero, so all six curves increased sharply at the beginning of the simulation. After 3 ps simulation, the force changes for the six systems were divided into two trends. The curves A, B, and C go up with the SMD time, which means that the LRAP groups were still adsorbed on the HAP surface. To pull the protein away from HAP, the applied force was increased to overcome the adsorption interactions. On the other hand, three curves D, E, and F decreased slightly, which demonstrates that the LRAP was desorbed. Because the external force broke the structure of LRAP violently, the bonds inside LRAP molecule and the interactions between LRAP and HAP change frequently, as many peaks can be observed in Figure 3. The molecular graphics package VMD47 was employed to analyze the static and dynamic structure information. The PCV
Adsorption of LRAP on Hydroxyapatite (001) Surface
J. Phys. Chem. C, Vol. 111, No. 3, 2007 1287
Figure 4. (A1, B1, and C1) VMD snapshots of the final states of three adsorption cases after 20 ps PCV simulation. Water molecules were omitted for clarity. (A2, B2, and C2) The distances between the marked atoms of LRAP and the HAP (001) surface in the c-axis with respect to SMD time.
results of the six cases were different, and LRAP was pulled away from the HAP surface or kept adsorbed on HAP as VMD snapshots displayed in Figures 4 and 5. There are two types of calcium ions, denoted as CA1 and CA2 in the HAP crystal. In these simulations, the outermost layer of HAP anear LRAP was occupied by CA1. In the following snapshots in Figures 4 and 5, the oxygen, hydrogen, and calcium ions were marked with red, white, and cyan colors, respectively. At the initial of SMD, the marked oxygen and hydrogen atoms were very close to the HAP surface. (3) Adsorption Cases. Different orientations of LRAP lead to different atomic groups being exposed to the HAP surface and may exhibit different adsorption behaviors. Among all six different orientations, in the A, B, and C cases, carboxyl oxygen atoms adsorbed on the HAP surface, as shown in Figure 4. In the case of A, two -COO- terminuses of residues Asp59 and Glu57 are bound tightly on the HAP (001) surface during the simulation, while other groups were drawn away from their original positions by the external force. From A1 shown in Figure 4, one could see explicitly that four oxygen atoms of carboxyl groups were much closer to the HAP surface than were other atoms. The distances between the four oxygen atoms and the HAP surface in the c-axis direction were measured then. As shown in Figure 4A2, the distances from two oxygen atoms
of residue Asp59 to the HAP surface were greater than those of residue Glu57. As the strength of electrostatic interaction is closely related to the action range, the distance of carboxyl oxygen of Glu57 fluctuated more gently than that of Asp59. A broad peak was observed for Asp59 before 7.5 ps (Figure 4A2), which could be explained by the observation of trajectory. It could be clearly found that the carboxyl oxygen atoms of Asp59 had the trend to be pulled away at first in the trajectory. However, they were adjacent to adsorbed Glu57, and hence they were drawn back finally. In this case, the external force was strong enough to denature the secondary structure of LRAP. However, the distances from each of these four atoms to the HAP crystal are in a short range, and they were able to resist the disturbance during the whole simulation, which indicated a strong interaction between them. This result suggests that the adsorption strength was stronger than or at least as strong as the external force in this simulation. The carboxyl oxygen atoms of Glu18 in case B grasped the HAP tightly during the whole simulation, as shown in Figure 4B1. From Figure 4B2, it could be found that the two curves of distance between oxygen atoms and the HAP surface went up slightly in the end. This indicates that these two oxygen atoms might be desorbed finally, which was consistent with the observation of trajectory. With respect to case C, two carboxyl oxygen atoms of residue Asp59 were
1288 J. Phys. Chem. C, Vol. 111, No. 3, 2007
Chen et al.
Figure 5. (D1, E1, and F1) VMD snapshots of the final states of three desorption cases after 20 ps PCV simulation. Water molecules were omitted for clarity. (D2, E2, and F2) The distances between the marked atoms of LRAP and the HAP (001) surface in the c-axis with respect to SMD time.
attracted to the calcium ion of HAP firmly all of the time. The final state of this case was shown in Figure 4C1. It is interesting to notice that an oxygen atom of residue Pro7, which was also close to the HAP surface at beginning, was pulled away from the surface in the end, as shown in Figure 4C2. The distinctive difference shows that the interaction strength offered by at least two oxygen atoms can resist the external force. In these three adsorption cases, carboxyl groups kept close to HAP surface during all simulations. Both of the two carboxyl oxygen atoms interacted with the calcium ion through the Coulombic force and formed a triangle structure. Here, we concluded that carboxyl groups could be adsorbed on HAP firmly, but it did not mean that every carboxyl group could be adsorbed effectively. The location of the carboxyl groups is an important factor. First, the two carboxyl oxygen atoms should be located on the site pointing directly to the calcium ion of HAP. Only in this way could the three atoms could form a triangle structure and could the electrostatic interaction among them resist external disturbances. In fact, this triangle structure is a collaborated system. Second, the oxygen atoms should be close enough to the calcium ion. Because the Coulombic force is in inverse proportion to the square of distance, it is only in a short distance range that the adsorption force can resist the external disturbances. Electrostatic interaction in short distance
is much greater than the van der Waals (VDW) interaction and the H-bond interaction. Furthermore, the protein structure also plays an important role in the adsorption. The carboxyl-rich structure increases the adsorption possibility. LRAP has many Glu and Asp residues, and they are the only two acidic amino acids that contain carboxyl at both ends among all 20 amino acids. In our simulation systems, residue Asp59 lies in the C-terminal of LRAP with two unbonded carboxyls. In cases A, C, and E, Asp59 was observed to be exposed to the HAP (001) surface. (4) Desorption Cases. In the other three orientations (cases D, E, and F), no atomic groups finally adsorbing tightly on the HAP surface were observed after the SMD simulations. In the original state of case D, few oxygen atoms are close to the HAP surface. LRAP interacted with the HAP surface mainly through the hydrogen atoms, and the whole protein molecule desorbed after 20 ps PCV simulation (Figure 5D). In case E, LRAP had both carbonyl and carboxyl oxygen atoms on the surface oriented to HAP; however, they could not catch HAP in the end. Although the carboxyl oxygen atoms of Asp59 were close to the HAP surface, LRAP finally desorbed, as shown in Figure 5E. The oxygen atoms adsorbed on HAP in adsorption systems should be located directly to the calcium ion, but in this system they were located at the sites, which were away from the calcium
Adsorption of LRAP on Hydroxyapatite (001) Surface ion. However, if the carboxyl oxygen atoms were not near to the calcium ion of HAP, the strong interaction could not be effectively formed to resist the external force. There were also many oxygen atoms on the LRAP surface exposed to HAP in case F. Yet, because of the structure character of LRAP, all of these oxygen atoms were far away from the surface. Hydrogen atoms of alkyl and amido, which were the closest to the HAP surface, could not form the adsorption interaction strong enough to avoid protein from desorbing (Figure 5F). In these desorption cases, hydrogen atoms existed much closer to HAP than oxygen atoms at the original states, and no strong interactions formed. In fact, not only oxygen but also hydrogen and other atoms of LRAP could interact with the HAP crystal.20 It is discerned from Figure 5D2 and F2 that the interaction between the hydrogen atoms and the HAP fought against the external force for 5 and 8 ps, respectively. This proved that the hydrogen atoms also contributed to the adsorption. Yet, because the force strength between them is relatively weak, the interactions caused by other atoms became subordinate. For example, the carboxyl oxygen atoms at the same distance could resist the external force during the whole simulation as shown in Figure 4A2 and C2. Furthermore, the distribution of surface charge was also important for the adsorption. Calcium cations occupied the outmost layer of the HAP (001) surface in the c-axis, resulting in the fact that oxygen anions were prone to be adsorbed on the HAP surface. Although hydrogen atoms also had the interaction with the HAP crystal, the residue -PO43was far away from them. It rendered the strength of this interaction to be smaller than that of oxygen. Conclusively, the Coulombic interaction between the carboxyl oxygen atoms and the calcium ions dominated the adsorption between LRAP and HAP in the simulations. Briefly, among all six orientations of LRAP, in cases A, B, and C, LRAP surfaces exposed carboxyl groups to the HAP surface and these groups bound tightly to the HAP surface, while in cases D, E, and F, protein surfaces that were exposed to HAP lacked carboxyl groups. It led to the fact that three faces of LRAP could grasp the HAP (001) surface despite the disturbance of the external forces, while the other three desorbed. Also, the interaction between carboxyl groups and calcium ions of HAP, especially the triangle structure, contributed mainly to the protein adsorption. In the triangle interaction form, two carboxyl oxygen atoms were just like a claw to grasp the calcium cation tightly. As soon as the -COO- claws met a calcium cation in an apropos position, they would seize it firmly. LRAP has many such claws distributing in the whole protein, so it could be adsorbed on the HAP in the different directions. It worked like glue that could agglutinate the HAP crystal together. Through the AFM experiments, amelogenin had been found to exist both in the matrix substrate and in the interstice between HAP crystals.13 The interaction mode of LRAP with the HAP surface described by claws and glue suggested by our simulation might provide some insight into the reason that amelogenin could graduate and elongate the growth of HAP, which had been proved by some experiments and medical practices. Conclusion Many proteins could graduate the nucleation and development of the HAP crystals in vivo, which is of importance in both academics and medical applications. However, the reason that certain proteins (e.g., LRAP, BMP-2, and BMP-7) could affect the growth of HAP and the detailed interaction mechanism are still unclear. In this work, we demonstrated a detailed simulation of adsorption mechanism for a typical graduating protein, LRAP,
J. Phys. Chem. C, Vol. 111, No. 3, 2007 1289 on the HAP (001) surface in a controlled way. Energy minimization and equilibrium MD simulation were carried out to obtain the stable states. Through a series of SMD investigations, it was found that the strong adsorption groups of LRAP were indeed located at the hydrophilic C-terminus as suggested by the experiments. However, it did not mean the N-terminus and the middle portion of LRAP had no interaction with HAP. Because the HAP (001) surface is occupied by calcium ions, the electrostatic effect between -COO- and the HAP is much greater than other interactions in the simulations. The most notable finding is that the -COO- claw of LRAP grasps the calcium ion with its two oxygen atoms in a triangle form. This interaction form can resist external force to some extent and is the key factor of the adsorption between LRAP and HAP from simulation results. A series of simulations and AFM experiments are being carried out in our group. From our studies and related literature,48,49 it was found that there are many factors influencing the interaction between proteins and the HAP surface, such as the protein structures, the ratio of Ca/P on the surface, the defect of HAP crystals, the charge distribution of HAP surface, the effect of water molecules, pH value, and so on. Several different adsorption modes had been observed. We would like to point out that the interaction mode of -COO- claw grasping calcium ion is just one of these adsorption forms. It would be helpful to clarify the understanding of the mechanism that amelogenin protein graduates the development of dental enamel, which is interesting in the fields of interfacial chemistry of protein-solid and biomineralization. Acknowledgment. This work was financially supported by the National Natural Science Foundation of China (grant nos. 60533050 and 20503025). Supporting Information Available: Convergence details of SMD parameters (pulling velocity V and spring constant k). This material is available free of charge via the Internet at http:// pubs.acs.org. References and Notes (1) Ahn, E. S.; Gleason, N. J.; Nakahira, A.; Ying, J. Y. Nano Lett. 2001, 1, 149. (2) Habelitz, S.; Kullar, A.; Marshall, S. J.; DenBesten, P. K.; Balooch, M.; Marshall, G. W.; Li, W. J. Dent. Res. 2004, 83, 698. (3) Kandori, K.; Masunari, A.; Ishikawa, T. Calcif. Tissue Int. 2005, 76, 194. (4) Gray, J. J. Curr. Opin. Struct. Biol. 2004, 14, 110. (5) Shaw, W. J.; Campbell, A. A.; Paine, M. L.; Snead, M. L. J. Biol. Chem. 2004, 279, 40263. (6) Zurlinden, K.; Laub, M.; Jennissen, H. P. Materialwiss. Werkstofftech. 2005, 36, 820. (7) Simmer, J. P.; Fincham, A. G. Crit. ReV. Oral Biol. Med. 1995, 6, 84. (8) Hunter, G. K.; Hauschka, P. V.; Poole, A. R.; Rosenberg, L. C.; Goldberg, H. A. Biochem. J. 1996, 317, 59 (9) Du, C.; Falini, G.; Fermani, S.; Abbott, C.; Moradian-Oldak, J. Science 2005, 307, 1450. (10) Kirkham, J.; Brookes, S. J.; Shore, R. C.; Wood, S. R.; Smith, D. A.; Zhang, J.; Chen, H.; Robinson, C. Curr. Opin. Colloid Interface Sci. 2002, 7, 124. (11) Minton, A. P. Biophys. J. 1999, 76, 176. (12) Smith, C. E.; Nancy, A. Anat. Rec. 1996, 245, 186. (13) Wen, H. B.; Fincham, A. G.; Moradian-Oldak, J. Matrix Biol. 2001, 20, 387. (14) Long, J. R.; Shaw, W. J.; Stayton, P. S.; Drobny, G. P. Biochemistry 2001, 40, 15451. (15) Shaw, W. J.; Long, J. R.; Dindot, J. L.; Campbell, A. A.; Stayton, P. S.; Drobny, G. P. J. Am. Chem. Soc. 2000, 122, 1709. (16) Stayton, P. S.; Drobny, G. P.; Shaw, W. J.; Long, J. R.; Gilbert, M. Crit. ReV. Oral Biol. Med. 2003, 14, 370.
1290 J. Phys. Chem. C, Vol. 111, No. 3, 2007 (17) Wallwork, M. K.; Kirkham, J.; Zhang, J.; Smith, D. A.; Brookes, S. J.; Shore, R. C.; Wood, S. R.; Ryu, O.; Robinson, C. Langmuir 2001, 17, 2508. (18) Moradian-Oldak, J.; Tan, J.; Fincham, A. G. Biopolymers 1998, 46, 225. (19) Bouropoulos, N.; Moradian-Oldak, J. Calcif. Tissue Int. 2003, 72, 599. (20) Milan, A. M.; Sugars, R. V.; Embery, G.; Weddington, R. J. Eur. J. Oral Sci. 2006, 114, 22. (21) Gilbert, M.; Shaw, W. J.; Long, J. R.; Nelson, K.; Drobny, G. P.; Giachelli, C. M.; Stayton, P. S. J. Biol. Chem. 2000, 275, 16213. (22) Raghunathan, V.; Gibson, J. M.; Goobes, G.; Popham, J. M.; Louie, E. A.; Stayton, P. S.; Drobny, G. P. J. Phys. Chem. B 2006, 110, 9324. (23) Moradian-Oldak, J.; Bouropoulos, N.; Wang, L.; Gharakhanian, N. Matrix Biol. 2002, 21, 197. (24) Raffaini, G.; Ganazzoli, F. Langmuir 2004, 20, 3371. (25) Raffaini, G.; Ganazzoli, F. Langmuir 2003, 19, 3403. (26) Zhou, J.; Chen, S.; Jiang, S. Langmuir 2003, 19, 3472. (27) Agashe, M.; Raut, V.; Stuart, S. J.; Latour, R. A. Langmuir 2005, 21, 1103. (28) Izrailev, S.; Stepaniants, S.; Isralewitz, B.; Kosztin, D.; Lu, H.; Molnar, F.; Wriggers, W.; Schulten, K. Computational Molecular Dynamics. Challenges, Methods, Ideas, Vol. 4. In Lecture Notes in Computational Science and Engineering; Deuflhard, P., Hermans, J., Leimkuhler, B., Mark, A. E., Reich, S., Skeel, R. D., Eds.; Springer-Verlag: Berlin, 1998; p 39. (29) Isralewitz, B.; Baudry, J.; Gullingsrud, J.; Kosztin, D.; Schulten, K. J Mol. Graphics Modell. 2001, 19, 13. (30) Isralewitz, B.; Gao, M.; Schulten, K. Curr. Opin. Struct. Biol. 2001, 11, 224. (31) Onuma, K.; Kanzaki, N.; Ito, A.; Tateishi, T. J. Phys. Chem. B 1998, 102, 7833. (32) Duffy, D. M.; Harding, J. H. Langmuir 2004, 20, 7637. (33) Pan, H. H.; Tao, J. H.; Wu, T.; Tang, R. K. Chin. J. Inorg. Chem. 2006, 22, 1392. (34) Fincham, A. G.; Moradian-Oldak, J.; Diekwisch, T. G.; Lyaruu, D. M.; Wright, J. T.; Bringas, P., Jr.; Slavkin, H. C. J. Struct. Biol. 1995, 115, 50.
Chen et al. (35) Gonzalez-McQuire, R.; Chane-Ching, J. Y.; Vignaud, E.; Lebugle, A.; Mann, S. J. Mater. Chem. 2004, 14, 2277. (36) Geourjon, C.; Dele´age, G. Comput. Appl. Biosci. 1995, 11, 681. (37) Combet, C.; Blanchet, C.; Geourjon, C.; Dele´age, G. NPS@: Network Protein Sequence Analysis TIBS 2000, 25, 147. (38) Kale, L.; Skeel, R.; Bhandarkar, M.; Brunner, R.; Gursoy, A.; Krawetz, N.; Phillips, J.; Shinozaki, A.; Varadarajan, K.; Schulten, K. NAMD2: Greater scalability for parallel molecular dynamics. J. Comput. Phys. 1999, 151, 283. (39) Berendsen, H. J. C.; Postma, J. P. M.; van Gunsteren, W. F.; Hermans, J. Interaction Models for Water in Relation to Protein Hydration. In Intermolecular Forces; Pullman, B., Ed.; Reidel: Dordrecht, The Netherlands, 1981; pp 331-342. (40) MacKerell, A. D., Jr.; Bashford, D.; Bellott, M.; Dunbrack, R. L., Jr.; Evanseck, J. D.; Field, M. J.; Fischer, S.; Gao, J.; Guo, H.; Ha, S.; Joseph-McCarthy, D.; Kuchnir, L.; Kuczera, K.; Lau, F. T. K.; Mattos, C.; Michnick, S.; Ngo, T.; Nguyen, D. T.; Prodhom, B.; Reiher, W. E., III; Roux, B.; Schlenkrich, M.; Smith, J. C.; Stote, R.; Straub, J.; Watanabe, M.; Wio´rkiewicz-Kuczera, J.; Yin, D.; Karplus, M. J. Phys. Chem. B 1998, 102, 3586. (41) Wilson, R. M.; Elliott, J. C.; Dowker, S. E. P. Am. Mineral. 1999, 84, 1406. (42) Hauptmann, S.; Dufner, H.; Brickmann, J.; Kast, S. M.; Berry, R. S. Phys. Chem. Chem. Phys. 2003, 5, 635. (43) Hirschfelder, J. O.; Curtiss, C. F.; Brid, R. B. Molecular Theory of Gases and Liquids; John Wiley and Sons: New York, 1954. (44) Harding, J. H.; Duffy, D. M. J. Mater. Chem. 2006, 16, 1105. (45) Gao, H. J.; Kong, Y. Annu. ReV. Mater. Res. 2004, 34, 123. (46) Ravichandran, S.; Madura, J. D.; Talbot, J. J. Phys. Chem. B 2001, 105, 3610. (47) Humphrey, W.; Dalke, A.; Schulten, K. VMD-Visual Molecular Dynamics. J. Mol. Graphics 1996, 14, 33. (48) Zahn, D.; Hochrein, O. Z. Anorg. Allg. Chem. 2005, 631, 1134. (49) Zahn, D.; Hochrein, O. Phys. Chem. Chem. Phys. 2003, 5, 4004.
