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95
rectangular cell with the size of 66.73×61.88×60 Å, as shown in Fig 4.3.
Three-dimensional periodic boundary conditions (PBC) were applied. The initial
positions of water molecules were randomly assigned. Any water molecule within
3.0Å of the lysozyme molecule was removed. The size of the cell is larger than the
largest extent of the protein plus the cutoff . Cl- ions were added to neutralize the
system.
The simulation was performed in the NVT ensemble. Prior to MD simulation, the
system was energy minimized for 500 cycles, using the CG (Polak-Ribiere) algorithm
to remove the bad contacts between molecules followed by 30 ps of MD simulation
run. The system was pre-equilibrated with the time step of 1 fs, still fixing the
positions of protein atoms while the water molecules were allowed to move around
the protein. The initial velocities were assigned at 308 K from a Maxwell-Boltzmann
distribution. In the next step, the whole system was equilibrated for 0.584 ns,
continuing from the final coordinates of pre-equilibration of the first step but
reassigning the initial velocities of protein and water atoms at the same temperature
from a Maxwell-Bolzmann distribution at the same temperature 308 K. In this step,
the atoms of lysozyme were mobile except any covalent bonds containing hydrogen
atoms. These bonds involving hydrogen atoms were kept rigid using the Rattle
method with a relative geometric tolerance of 10-4 to remove the high frequent
vibrations of these bonds and to apply the larger time step of 2fs. When the system
was approaching the equilibrium state, the system was finally equilibrated, without
any constraints of the protein bonds, using the smaller time step of 1fs for 0.138 ns.
Object Description
| Title | Experimental study and atomic simulation of protein adsorption |
| Author | Wei, Tao |
| Author email | twei2004@gmail.com; dnaafm@yahoo.com.cn |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Chemical Engineering |
| School | Viterbi School of Engineering |
| Date defended/completed | 2008-07-29 |
| Date submitted | 2008 |
| Restricted until | Unrestricted |
| Date published | 2008-10-07 |
| Advisor (committee chair) | Shing, Katherine |
| Advisor (committee member) |
Nakano, Aiichiro Goo, Edward K. |
| Abstract | The studies of protein adsorption at solid-liquid interface are important in various applications. Multilayer and irreversible adsorption behaviors are commonly observed. In this work, protein adsorption behavior at the solid-liquid interface was investigated by a combination of experimental Fourier transform infrared/attenuated total reflectance (FTIR/ATR) studies and computer simulations: Molecular Dynamics (MD) simulation and hybrid Genetic-Algorithm (GA) schemes.; BSA, lysozyme, IgG and fibrinogen adsorption was studied with FTIR/ATR in tris(hydroxymethyl)-aminomethane hydrochloride (Tris-HCl) and phosphate buffered saline (PBS) buffers on a Ge surface. Buffer choice was shown to drastically affect adsorption kinetics. In comparison with Tris-HCl, PBS buffer depresses the adsorption of BSA, IgG and fibrinogen in the prolonged quasi-linear kinetic region while lysozyme adsorption is relatively insensitive to buffer choice. Buffer concentration can also significantly affect protein adsorption. The secondary structures in the adsorbed phase are generally quite different from the bulk structure; however, buffer choice has negligible effect on structural evolution. Significant secondary structure changes occur during adsorption. The secondary structures in the adsorbed phase are inhomogeneous. The role of phosphate ions in PBS buffer and their effect on protein adsorption are rather complex. Phosphate ions adsorb competitively against protein molecules and their deprotonation equilibrium can be altered at the solid-liquid interface due to the adsorbed protein.; The effect of surface on adsorption is examined by adsorbing IgG on various polymer-coated surfaces. IgG adsorption is higher on more hydrophobic surface. IgG molecules adsorbed in layers near hydrophilic solid surfaces suffer less secondary structure changes.; The behavior of lysozyme during adsorption on a hydrogen-terminated Si surface (Si-H) is studied using MD simulations. Although atomistic simulations are highly time-consuming for direct observations of complete secondary structure changes, indications of molecular deformations are observed over nanosecond simulation time scale. Lysozyme molecule undergoes deformation onto the Si-H surface, as is evidenced by the reduction in the volume, the increase in solvent accessible surface area, the change of the overall shape, and certain amount of alteration in secondary structures. The main α-helix domains experience some loss while the beta-sheet domains remain almost intact. The hydrophobic character of the surface is believed to contribute to the loss of the organized structures of the amino residues in close proximity to the surface.; An efficient hybrid GA/spatial-grid method was developed to search for low adsorption-energy orientations and locations of a protein molecule on a solid surface. The surface and the protein molecule are treated as rigid bodies, whereas the bulk fluid is represented by spatial grids. The hybrid search procedure consists of two interlinked loops. In 1st loop (A), a GA is employed to identify promising regions for the global energy minimum, whereas a local optimizer with the derivative-free Nelder-Mead method is used to search for the lowest-energy orientation within the identified regions. In 2nd loop (B), new population is generated and competitive solution from loop A is improved. The switching between two loops is adaptively controlled by similarity analysis. We test the method for lysozyme adsorption on a hydrophobic Si-H (110) surface in implicit water. The hybrid search method was shown to have faster convergence and better solution accuracy compared with the conventional GA, which suffered from premature convergence. |
| Keyword | protein adsorption; FTIR/ATR; MD simulation; hybrid genetic algorithm |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Provenance | Electronically uploaded by the author |
| Type | texts |
| Legacy record ID | usctheses-m1641 |
| Contributing entity | University of Southern California |
| Rights | Wei, Tao |
| Repository name | Libraries, University of Southern California |
| Repository address | Los Angeles, California |
| Repository email | cisadmin@lib.usc.edu |
| Filename | etd-Wei-2367 |
| Archival file | uscthesesreloadpub_Volume14/etd-Wei-2367.pdf |
Description
| Title | Page 111 |
| Contributing entity | University of Southern California |
| Repository email | cisadmin@lib.usc.edu |
| Full text | 95 rectangular cell with the size of 66.73×61.88×60 Å, as shown in Fig 4.3. Three-dimensional periodic boundary conditions (PBC) were applied. The initial positions of water molecules were randomly assigned. Any water molecule within 3.0Å of the lysozyme molecule was removed. The size of the cell is larger than the largest extent of the protein plus the cutoff . Cl- ions were added to neutralize the system. The simulation was performed in the NVT ensemble. Prior to MD simulation, the system was energy minimized for 500 cycles, using the CG (Polak-Ribiere) algorithm to remove the bad contacts between molecules followed by 30 ps of MD simulation run. The system was pre-equilibrated with the time step of 1 fs, still fixing the positions of protein atoms while the water molecules were allowed to move around the protein. The initial velocities were assigned at 308 K from a Maxwell-Boltzmann distribution. In the next step, the whole system was equilibrated for 0.584 ns, continuing from the final coordinates of pre-equilibration of the first step but reassigning the initial velocities of protein and water atoms at the same temperature from a Maxwell-Bolzmann distribution at the same temperature 308 K. In this step, the atoms of lysozyme were mobile except any covalent bonds containing hydrogen atoms. These bonds involving hydrogen atoms were kept rigid using the Rattle method with a relative geometric tolerance of 10-4 to remove the high frequent vibrations of these bonds and to apply the larger time step of 2fs. When the system was approaching the equilibrium state, the system was finally equilibrated, without any constraints of the protein bonds, using the smaller time step of 1fs for 0.138 ns. |
