Full Text Available
Note: Clicking the button above will open the full text document at the original institutional repository in a new window.
The development of hybrid quantum classical computational methods for carbohydrate and hypervalent phosphoric systems
Includes bibliographical references.
Saved in:
| Main Author: | |
|---|---|
| Other Authors: | |
| Format: | Thesis |
| Language: | English |
| Published: |
Department of Chemistry
2015
|
| Subjects: | |
| Tags: |
No Tags, Be the first to tag this record!
|
| _version_ | 1867613212323610624 |
|---|---|
| access_status_str | Open Access |
| author | Govender, Krishna Kuben |
| author2 | Naidoo, Kevin J |
| author_browse | Govender, Krishna Kuben Naidoo, Kevin J |
| author_facet | Naidoo, Kevin J Govender, Krishna Kuben |
| author_sort | Govender, Krishna Kuben |
| collection | Thesis |
| description | Includes bibliographical references. |
| format | Thesis |
| id | oai:open.uct.ac.za:11427/13297 |
| institution | University of Cape Town (South Africa) |
| language | eng |
| last_indexed | 2026-06-10T12:32:33.381Z |
| license_str | Not specified — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UCTD — University of Cape Town Open Access Repository |
| publishDate | 2015 |
| publishDateRange | 2015 |
| publishDateSort | 2015 |
| publisher | Department of Chemistry |
| publisherStr | Department of Chemistry |
| record_format | dspace |
| source_str | UCTD — University of Cape Town Open Access Repository |
| spelling | oai:open.uct.ac.za:11427/13297 The development of hybrid quantum classical computational methods for carbohydrate and hypervalent phosphoric systems Govender, Krishna Kuben Naidoo, Kevin J Venter, Gerhard Chemistry Includes bibliographical references. Ab initio, density functional theory, and semi-empirical methods serve as major computational tools for quantum mechanical calculations of medium to large molecular systems. Semi-empirical methods are most effectively used in a hybrid quantum mechanics/molecular mechanics (QM/MM) dynamics framework. However, semi-empirical methods have been designed to provide accurate results for organic molecules, but often fail to treat hypervalent species accurately due to their use of an sp basis. Recently, significant breakthroughs have been made with the incorporation of d-orbitals into the semi-empirical framework, thereby allowing for accurate modeling of both hypervalent and transition metal systems. Here I consider two methods that adopt this new methodology, namely AM1/d-PhoT and AM1*. Our major focus is the simulation of chemical biological and more specifically chemical glycobiological problems of biochemical interest. When I tested the ability of both AM1/d-PhoT and AM1* to reproduce key metrics in chemical glycobiology (i.e., sugar ring pucker, phosphate participation in transferase reactions) these methods, in combination with the published parameters, performed very poorly. Using the AM1/d-PhoT and AM1* Hamiltonians I set out to re-parameterize these methods aiming to produce holistic biochemical QM/MM toolsets able to simulate fundamental problems of binding and enzyme reactivity in chemical glycobiology. We called these methods AM1/d-CB1 and AM1*-CB1. In the development of these parameter sets I focused specifically on proton transfer, carbohydrate ring puckering, bond polarization, amino acid interactions, and phosphate interactions (facets important to chemical glycobiology). Both AM1/d-CB1 and AM1*-CB1 make use of a variable property optimization parameter approach for the glycan molecular class and its chemical environment. The accuracy of these methods is evaluated for carbohydrates, amino acids and phosphates present in catalytic domains of glycoenzymes, and the are shown to be more accurate for key performance indices (puckering, etc.) and on average across all simulation derived properties (QM/MM polarization, protein performance, etc.) than all other NDDO semiempirical methods currently being used. A major objective of the newly developed AM1/d-CB1 and AM1*-CB1 is to provide a platform to accurately model reactions central to chemical glycobiology using hybrid QM/MM molecular dynamics (MD) simulations. AM1/d-CB1 is applied to a well-known reaction involving purine nucleoside phosphorylase (PNP) and results lead me to conclude that the method shows promise for modelling glycobiological QM/MM systems. 2015-07-02T08:44:18Z 2015-07-02T08:44:18Z 2014 Doctoral Thesis Doctoral PhD http://hdl.handle.net/11427/13297 eng application/pdf Department of Chemistry Faculty of Science University of Cape Town |
| spellingShingle | Chemistry Govender, Krishna Kuben The development of hybrid quantum classical computational methods for carbohydrate and hypervalent phosphoric systems |
| thesis_degree_str | Doctoral |
| title | The development of hybrid quantum classical computational methods for carbohydrate and hypervalent phosphoric systems |
| title_full | The development of hybrid quantum classical computational methods for carbohydrate and hypervalent phosphoric systems |
| title_fullStr | The development of hybrid quantum classical computational methods for carbohydrate and hypervalent phosphoric systems |
| title_full_unstemmed | The development of hybrid quantum classical computational methods for carbohydrate and hypervalent phosphoric systems |
| title_short | The development of hybrid quantum classical computational methods for carbohydrate and hypervalent phosphoric systems |
| title_sort | development of hybrid quantum classical computational methods for carbohydrate and hypervalent phosphoric systems |
| topic | Chemistry |
| url | http://hdl.handle.net/11427/13297 |
| work_keys_str_mv | AT govenderkrishnakuben thedevelopmentofhybridquantumclassicalcomputationalmethodsforcarbohydrateandhypervalentphosphoricsystems AT govenderkrishnakuben developmentofhybridquantumclassicalcomputationalmethodsforcarbohydrateandhypervalentphosphoricsystems |