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You searched for subject:(beta CASP). Showing records 1 – 3 of 3 total matches.

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Texas A&M University

1. Qu, Xiaotao. A Molecular Mechanics Knowledge Base Applied to Template Based Structure Prediction.

Degree: 2011, Texas A&M University

Predicting protein structure using its primary sequence has always been a challenging topic in biochemistry. Although it seems as simple as finding the minimal energy conformation, it has been quite difficult to provide an accurate yet reliable solution for the problem. On the one hand, the lack of understanding of the hydrophobic effect as well as the relationship between different stabilizing forces, such as hydrophobic interaction, hydrogen bonding and electronic static interaction prevent the scientist from developing potential functions to estimate free energy. On the other hand, structure databases are limited with redundant structures, which represent a noncontinuous, sparsely-sampled conformational space, and preventing the development of a method suitable for high-resolution, high-accuracy structure prediction that can be applied for functional annotation of an unknown protein sequence. Thus, in this study, we use molecular dynamics simulation as a tool to sample conformational space. Structures were generated with physically realistic conformations that represented the properties of ensembles of native structures. First, we focused our study on the relationship among different factors that stabilize protein structure. Using a wellcharacterized mutation system of the B-hairpin, a fundamental building block of protein, we were able to identify the effect of terminal ion-pairs (salt-bridges) on the stability of the beta-hairpin, and its relationship with hydrophobic interactions and hydrogen bonds. In the same study, we also correlated our theoretical simulations qualitatively with experimental results. Such analysis provides us a better understanding of beta-hairpin stability and helps us to improve the protein engineering method to design more stable hairpins. Second, with large-scale simulations of different representative protein folds, we were able to conduct a fine-grained analysis by sampling the continuous conformational space to characterize the relationship among backbone conformation, side-chain conformation and side-chain packing. Such information is valuable for improving high-resolution structure prediction. Last, with this information, we developed a new prediction algorithm using packing information derived from the conserved relative packing groups. Based on its performance in CASP7, we were able to draw the conclusion that our simulated dataset as well as our packing-oriented prediction method are useful for template based structure prediction. Advisors/Committee Members: Tsai, Jerry (advisor), Scholtz, Martin (advisor), Sacchettini, James (committee member), Polymenis, Michael (committee member).

Subjects/Keywords: structure prediction; molecular dynamics; casp; protein packing; beta hairpin

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APA (6th Edition):

Qu, X. (2011). A Molecular Mechanics Knowledge Base Applied to Template Based Structure Prediction. (Thesis). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/ETD-TAMU-2009-12-7234

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Qu, Xiaotao. “A Molecular Mechanics Knowledge Base Applied to Template Based Structure Prediction.” 2011. Thesis, Texas A&M University. Accessed June 17, 2019. http://hdl.handle.net/1969.1/ETD-TAMU-2009-12-7234.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Qu, Xiaotao. “A Molecular Mechanics Knowledge Base Applied to Template Based Structure Prediction.” 2011. Web. 17 Jun 2019.

Vancouver:

Qu X. A Molecular Mechanics Knowledge Base Applied to Template Based Structure Prediction. [Internet] [Thesis]. Texas A&M University; 2011. [cited 2019 Jun 17]. Available from: http://hdl.handle.net/1969.1/ETD-TAMU-2009-12-7234.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Qu X. A Molecular Mechanics Knowledge Base Applied to Template Based Structure Prediction. [Thesis]. Texas A&M University; 2011. Available from: http://hdl.handle.net/1969.1/ETD-TAMU-2009-12-7234

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation


McMaster University

2. Buzon, Beverlee D. Functional studies of the interstrand cross-link repair protein, SNM1A and its beta-CASP domain.

Degree: MSc, 2012, McMaster University

Interstrand cross-linking (ICL) damage to DNA is cytotoxic as it blocks replication and transcription. This cytotoxicity is exploited in anti-cancer therapies, but increased ICL repair limits the efficacy of these chemotherapies. SNM1A (sensitive to nitrogen mustard 1A), of the beta-CASP family of nucleases, has been shown to participate in the initiation of one of the ICL repair processes. Biochemical studies of SNM1A have been limited due to insolubility and instability of SNM1A in bacteria and insect cell lines and toxicity in human cell lines. Work reported in this thesis describes a novel and efficient method of generating active protein from inclusion body expression of the beta-CASP domain of SNM1A. This refolded beta-CASP domain shows 5’ exonuclease activity on single stranded and double stranded DNA in vitro. Nevertheless, this domain alone is unable to complement pso2 null ICL repair defects in S. cerevisiae after exposure to ICL agents. These functional studies of the beta-CASP domain of SNM1A will be helpful in directing future research on its role in ICL repair. Additionally, this will aid future structural and inhibitor studies of this essential interstrand cross-link repair protein, SNM1A.

Master of Science (MSc)

Advisors/Committee Members: Junop, Murray, Russell Bishop, William Sheffield, Biochemistry.

Subjects/Keywords: SNM1A; interstrand crosslink repair; beta-CASP; inclusion body protein refolding; nuclease; cisplatin; Biochemistry; Biochemistry

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Buzon, B. D. (2012). Functional studies of the interstrand cross-link repair protein, SNM1A and its beta-CASP domain. (Masters Thesis). McMaster University. Retrieved from http://hdl.handle.net/11375/12675

Chicago Manual of Style (16th Edition):

Buzon, Beverlee D. “Functional studies of the interstrand cross-link repair protein, SNM1A and its beta-CASP domain.” 2012. Masters Thesis, McMaster University. Accessed June 17, 2019. http://hdl.handle.net/11375/12675.

MLA Handbook (7th Edition):

Buzon, Beverlee D. “Functional studies of the interstrand cross-link repair protein, SNM1A and its beta-CASP domain.” 2012. Web. 17 Jun 2019.

Vancouver:

Buzon BD. Functional studies of the interstrand cross-link repair protein, SNM1A and its beta-CASP domain. [Internet] [Masters thesis]. McMaster University; 2012. [cited 2019 Jun 17]. Available from: http://hdl.handle.net/11375/12675.

Council of Science Editors:

Buzon BD. Functional studies of the interstrand cross-link repair protein, SNM1A and its beta-CASP domain. [Masters Thesis]. McMaster University; 2012. Available from: http://hdl.handle.net/11375/12675


McMaster University

3. Buzon, Beverly Diana. Characterization and inhibition of interstrand crosslink repair nuclease SNM1A.

Degree: PhD, 2018, McMaster University

Interstrand cross-links (ICLs) are a type of DNA damage that prevents strand separation required for basic cellular processes. ICL-based anti-cancer therapies exploit the cytotoxic consequences of replication and transcription inhibition, however, they are limited by the ability of the cell to repair DNA crosslinks. The challenge of ICL repair involves coordinating multiple DNA repair pathways to remove damage occurring on both strands of DNA. Participation of factors that are both exclusive and essential to crosslink repair suggests a pathway requirement to process unique structures and/or intermediates arising only in ICL repair. SNM1A is a nuclease required for survival of human cells in response to ICL exposure, but the specific function and role of SNM1A remain unclear. Here we show that, in addition to known 5’-3’exonuclease activity, SNM1A possesses single-strand specific endonuclease activity. Furthermore, SNM1A exhibits translesion nuclease activity on crosslinks which deform the helical backbone, but not non-distorting stable ICLs. We report the identification and characterization of nine small molecules inhibitors of SNM1A, isolated from an in vitro high-throughput screen of nearly 4,000 bioactive compounds. Finally, we demonstrate that inhibitors of SNM1A potentiate the cytotoxicity of ICL-inducing agent cisplatin in HeLa cells. The work in this thesis expands the possible roles of SNM1A in ICL repair and lays the groundwork for SNM1A inhibition in ICL sensitization efforts.

Thesis

Doctor of Philosophy (PhD)

Advisors/Committee Members: Junop, Murray, Biochemistry and Biomedical Sciences.

Subjects/Keywords: SNM1A; beta-CASP nuclease; small molecule inhibitors; translesion nuclease; chemoresistance; structure-specific endonuclease; interstrand crosslinking repair; high throughput screening

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Buzon, B. D. (2018). Characterization and inhibition of interstrand crosslink repair nuclease SNM1A. (Doctoral Dissertation). McMaster University. Retrieved from http://hdl.handle.net/11375/22872

Chicago Manual of Style (16th Edition):

Buzon, Beverly Diana. “Characterization and inhibition of interstrand crosslink repair nuclease SNM1A.” 2018. Doctoral Dissertation, McMaster University. Accessed June 17, 2019. http://hdl.handle.net/11375/22872.

MLA Handbook (7th Edition):

Buzon, Beverly Diana. “Characterization and inhibition of interstrand crosslink repair nuclease SNM1A.” 2018. Web. 17 Jun 2019.

Vancouver:

Buzon BD. Characterization and inhibition of interstrand crosslink repair nuclease SNM1A. [Internet] [Doctoral dissertation]. McMaster University; 2018. [cited 2019 Jun 17]. Available from: http://hdl.handle.net/11375/22872.

Council of Science Editors:

Buzon BD. Characterization and inhibition of interstrand crosslink repair nuclease SNM1A. [Doctoral Dissertation]. McMaster University; 2018. Available from: http://hdl.handle.net/11375/22872

.