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80
active sites, the mass distribution and the protein secondary structure can be
monitored using a simulation. Parameters, such as the radius of gyration, eccentricity,
asphericity, and prolateness 1, 2 are often used to quantify the size and the shape. The
Root Mean Square Deviation (RMSD) of the whole molecule and of each residue are
applied to quantify the mobility of the protein and amino residues and to verify the
stability of the system.
The secondary structural changes of neutral or charged protein subdomains were
studied by Raffainni and Ganazzoli.2-5 A series of simulations were carried out to
investigate the effects of the surface hydrophobicity or hydrophilicity (graphite
surface) and hydrophilic surface of poly (vinyl alcohol) on the protein fragments
without adding counter ions in effective continuum dielectric medium with a
distance-dependent dielectric constant corresponding to water ( = 78). Fragments of
globular protein with -helix structure, fibronectin with -sheet structure and a fibrous
protein with a triple-helix polypeptide were selected as model polypeptides for
studying the adsorption behavior. It was reported that there are some pronounced
parallel ordering on hydrophobic graphite surface, however, the formation of a new
secondary structure consisting of -sheet was not be observed in their simulations,
within nanosecond time scale.
The time scale of the mobility of protein subdomain as in comparison with the
internal structural rearrangement was studied by Latour et al. 6 Fibrinogen -chain
fragment was simulated on charged SAM surfaces with different functional groups,
derived from molecular models of S-(CH2)15-CH3 alkanethiol SAMs on a simulated
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 96 |
| Contributing entity | University of Southern California |
| Repository email | cisadmin@lib.usc.edu |
| Full text | 80 active sites, the mass distribution and the protein secondary structure can be monitored using a simulation. Parameters, such as the radius of gyration, eccentricity, asphericity, and prolateness 1, 2 are often used to quantify the size and the shape. The Root Mean Square Deviation (RMSD) of the whole molecule and of each residue are applied to quantify the mobility of the protein and amino residues and to verify the stability of the system. The secondary structural changes of neutral or charged protein subdomains were studied by Raffainni and Ganazzoli.2-5 A series of simulations were carried out to investigate the effects of the surface hydrophobicity or hydrophilicity (graphite surface) and hydrophilic surface of poly (vinyl alcohol) on the protein fragments without adding counter ions in effective continuum dielectric medium with a distance-dependent dielectric constant corresponding to water ( = 78). Fragments of globular protein with -helix structure, fibronectin with -sheet structure and a fibrous protein with a triple-helix polypeptide were selected as model polypeptides for studying the adsorption behavior. It was reported that there are some pronounced parallel ordering on hydrophobic graphite surface, however, the formation of a new secondary structure consisting of -sheet was not be observed in their simulations, within nanosecond time scale. The time scale of the mobility of protein subdomain as in comparison with the internal structural rearrangement was studied by Latour et al. 6 Fibrinogen -chain fragment was simulated on charged SAM surfaces with different functional groups, derived from molecular models of S-(CH2)15-CH3 alkanethiol SAMs on a simulated |
