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Thermodynamically Consistent Interatomic Potentials for Silica to Design Specifically Binding Peptides: Role of Surface Chemistry, PH, and Amino Acid Sequence

Emami, Fatemesadat
http://rave.ohiolink.edu/etdc/view?acc_num=akron1366597654

Abstract Details

2013, Doctor of Philosophy, University of Akron, Polymer Engineering.
Silica is commonplace in many industrial and laboratory-scale applications. However, control over the morphology of the silica particles has remained a major challenge. Nature exhibits examples of highly ornate silica-based materials produced under benign environmental conditions. For instance, marine microorganisms are able to condense silicic acid in-vivo in the presence of specific polypeptides and create a hierarchical siliceous frustule. Hence understanding the interactions of biological molecules in contact with silica can revolutionize the fabrication of tailored silica-based materials for specific applications. In this project, we pursued a systematic study of experimental and computational approaches to explain specific adsorption of peptides on silica particles. Silica surfaces exhibit sensitive surface chemistry with variable densities of silanol and siloxide groups depending on synthetic routes, pH, ionic strength, nanoparticle size, and other chemical and thermal treatments. In first approximation, amorphous silica can be described by Q3-type surfaces with approximately 4.7 silanol groups per square nanometer from which 0 to 20% are ionized depending on solution pH and ionic strength. We introduce a suite of models that captures realistic surface morphology and chemical functionality of silica in various chemical environments. Further, thermodynamically consistent intermolecular potentials compatible with common force fields such as CVFF, CHARMM, AMBER, PCFF, and COMPASS are presented. Bulk and interfacial properties including X-ray structure, IR-spectrum, density, heat of immersion, surface pressure, and surface wettability are reproduced in comparison to available experimental data. Experimental results of screening phage libraries on amorphous silica particles (biopanning experiment) show that peptides recognize the surface chemistry of the particles. Increasingly basic peptides preferred increasingly acidic silica particles, the surface structure of which was quantified by zeta potential measurements and acid-base titration. Subsequent examination of adsorption of the selected peptides by fluorometric assay and infrared spectroscopy followed by extensive molecular dynamics simulations indicated a distinct binding mechanism for cationic and non-cationic peptides. Positively charged peptides were strongly attracted to the particles by ion pairing of the positively charged moieties with surface siloxide groups. Adsorption levelled off at higher peptide concentration due to a rise in peptide-peptide electrostatic repulsion and possible reversal of the zeta potential. Non-cationic peptides were less strongly attracted to the particles by intermittent hydrogen bonds. Further, hydrophobic moieties tended to stay in the proximity of the surface due to exclusion from water with a strong hydrogen bond network. Point mutation of steric-restraining residues from the middle and end of the peptide showed significant change in the peptide conformation and binding. Peptide adsorption was also studied as a function of pH and particle size. The negative surface charge of silica increases at higher pH so that positively charged peptides are more strongly and negatively charged peptides less strongly recognized. Larger particles are more acidic at the interface, which can also alter the binding mechanism. Comparison of detected cross peaks of NOES by NMR experiment and inter-nuclear distances obtained from the simulation further confirms that molecular simulation with the new potentials is suited to monitor and predict conformations of peptides and other organic on aqueous silica surfaces.
Hendrik Heinz, Dr. (Advisor)
Jutta Luettmer-Strathmann, Dr. (Committee Member)
Thein Kyu, Dr. (Committee Member)
Ali Dhinojwala, Dr. (Committee Member)
Younjin Min, Dr. (Committee Member)
Jie Zheng, Dr. (Committee Member)
196 p.
Chemical Engineering; Chemistry; Molecular Biology; Molecular Chemistry; Molecular Physics; Petroleum Engineering; Pharmaceuticals; Pharmacy Sciences; Physics; Polymer Chemistry; Polymers

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Citations

  • Emami, F. (2013). Thermodynamically Consistent Interatomic Potentials for Silica to Design Specifically Binding Peptides: Role of Surface Chemistry, PH, and Amino Acid Sequence [Doctoral dissertation, University of Akron]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=akron1366597654

    APA Style (7th edition)

  • Emami, Fatemesadat. Thermodynamically Consistent Interatomic Potentials for Silica to Design Specifically Binding Peptides: Role of Surface Chemistry, PH, and Amino Acid Sequence. 2013. University of Akron, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=akron1366597654.

    MLA Style (8th edition)

  • Emami, Fatemesadat. "Thermodynamically Consistent Interatomic Potentials for Silica to Design Specifically Binding Peptides: Role of Surface Chemistry, PH, and Amino Acid Sequence." Doctoral dissertation, University of Akron, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=akron1366597654

    Chicago Manual of Style (17th edition)

akron1366597654
938
© 2013, all rights reserved.
This open access ETD is published by University of Akron and OhioLINK.