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89
MOLARIS and OPLS. With the advances in computation power in the past few
decades, several force fields have been developed to simulate protein behavior in
aqueous solution including CVFF, CHARMm, GROMOS and ESFF. The Consistent
Valence Force Field (CVFF) does not have an explicit term to account for polar, i.e.,
the diolar and quadropolar, interactions. The hydrogen bonds are included in the
Coulombic term, which is calculated by assigning partial charge for each atom. The
non-bond force field parameters, including the partial charge, were regressed by
least-square optimization of a large number of experimental crystal structures of
hydrocarbons, carboxylic acids, and amides, in addition to dipole moments and
sublimation energies, and were improved in some case by ab initio calculation.13 The
total energy consists of bonded and non-bonded energy. The bonded energy
contributions include terms for the bond stretching through the Morse potential, for
the bond angle and out-of-plane deformations, and for the torsional potentials. The
non-bonded interactions are accounted for through Lennard–Jones potentials for the
dispersive interactions and Coulombic terms for the electrostatic interactions between
integer or fractional charges for the electric dipoles.3
4.1.3 Research Objectives
MD simulation for lysozyme adsorption on H-terminated Si surface in aqueous
medium is conducted. Lysozyme is chosen because it has been extensive studied
experimentally and reliable structures are published. The Si-H surface is relatively
simple and can serve as a model hydrophobic surface. In the MD simulation, we will
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 105 |
| Contributing entity | University of Southern California |
| Repository email | cisadmin@lib.usc.edu |
| Full text | 89 MOLARIS and OPLS. With the advances in computation power in the past few decades, several force fields have been developed to simulate protein behavior in aqueous solution including CVFF, CHARMm, GROMOS and ESFF. The Consistent Valence Force Field (CVFF) does not have an explicit term to account for polar, i.e., the diolar and quadropolar, interactions. The hydrogen bonds are included in the Coulombic term, which is calculated by assigning partial charge for each atom. The non-bond force field parameters, including the partial charge, were regressed by least-square optimization of a large number of experimental crystal structures of hydrocarbons, carboxylic acids, and amides, in addition to dipole moments and sublimation energies, and were improved in some case by ab initio calculation.13 The total energy consists of bonded and non-bonded energy. The bonded energy contributions include terms for the bond stretching through the Morse potential, for the bond angle and out-of-plane deformations, and for the torsional potentials. The non-bonded interactions are accounted for through Lennard–Jones potentials for the dispersive interactions and Coulombic terms for the electrostatic interactions between integer or fractional charges for the electric dipoles.3 4.1.3 Research Objectives MD simulation for lysozyme adsorption on H-terminated Si surface in aqueous medium is conducted. Lysozyme is chosen because it has been extensive studied experimentally and reliable structures are published. The Si-H surface is relatively simple and can serve as a model hydrophobic surface. In the MD simulation, we will |
