- Title
- AMBER force field parameters for the Zn (II) ions of the tunneling-fold enzymes GTP cyclohydrolase I and 6-pyruvoyl tetrahydropterin synthase
- Creator
- Khairallah, Afrah
- Creator
- Tastan Bishop, Ozlem
- Creator
- Moses, Vuyani
- Subject
- To be catalogued
- Date Issued
- 2020
- Date
- 2020
- Type
- text
- Type
- article
- Identifier
- http://hdl.handle.net/10962/429360
- Identifier
- vital:72604
- Identifier
- xlink:href="https://doi.org/10.1080/07391102.2020.1796800"
- Description
- The folate biosynthesis pathway is an essential pathway for cell growth and survival. Folate derivatives serve as a source of the one-carbon units in several intracellular metabolic reactions. Rapidly dividing cells rely heavily on the availability of folate derivatives for their proliferation. As a result, drugs targeting this pathway have shown to be effective against tumor cells and pathogens, but drug resistance against the available antifolate drugs emerged quickly. Therefore, there is a need to develop new treatment strategies and identify alternative metabolic targets. The two de novo folate biosynthesis pathway enzymes, GTP cyclohydrolase I (GCH1) and 6-pyruvoyl tetrahydropterin synthase (PTPS), can provide an alternative strategy to overcome the drug resistance that emerged in the two primary targeted enzymes dihydrofolate reductase and dihydropteroate synthase. Both GCH1 and PTPS enzymes contain Zn2+ ions in their active sites, and to accurately study their dynamic behaviors using all-atom molecular dynamics (MD) simulations, appropriate parameters that can describe their metal sites should be developed and validated. In this study, force field parameters of the GCH1 and PTPS metal centers were generated using quantum mechanics (QM) calculations and then validated through MD simulations to ensure their accuracy in describing and maintaining the Zn2+ ion coordination environment. The derived force field parameters will provide accurate and reliable MD simulations involving these two enzymes for future in-silico identification of drug candidates against the GCH1 and PTPS enzymes.
- Format
- computer
- Format
- online resource
- Format
- application/pdf
- Format
- 1 online resource (18 pages)
- Format
- Publisher
- Taylor and Francis
- Language
- English
- Relation
- Journal of Biomolecular Structure and Dynamics
- Relation
- Khairallah, A., Tastan-Bishop, Ö. and Moses, V. (2020) AMBER force field parameters for the Zn (II) ions of the tunneling-fold enzymes GTP cyclohydrolase I and 6-pyruvoyl tetrahydropterin synthase. Journal of Biomolecular Structure and Dynamics. 2020 (2020). p.1-18
- Relation
- Journal of Biomolecular Structure and Dynamics volume 2020 p. 1 2020 1538-0254
- Rights
- Publisher
- Rights
- Use of this resource is governed by the terms and conditions of the Taylor and Francis Online Terms and Conditions Statement (https://www.tandfonline.com/terms-and-conditions)
- Rights
- Closed Access
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- Visitors: 124
- Downloads: 8
Collections
Tastan Bishop, Ozlem (Prof)
SDG 03. Good Health and Well-Being
RU Department of Biochemistry, Microbiology and Bioinformatics
| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | SOURCE1 | AMBER force field parameters for the Zn (II) ions of the tunneling-fold enzymes GTP cyclohydrolase.pdf | 818 KB | Adobe Acrobat PDF | View Details Download |