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Protein Structure and Design by Gene...

Rollins, Nathanael Jedidiah Reodica.

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Protein Structure and Design by Genetic Experiments.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Protein Structure and Design by Genetic Experiments./
Author:	Rollins, Nathanael Jedidiah Reodica.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2020,
Description:	186 p.
Notes:	Source: Dissertations Abstracts International, Volume: 82-06, Section: B.
Contained By:	Dissertations Abstracts International82-06B.
Subject:	Molecular biology. -
Online resource:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28151433
ISBN:	9798698539834

Protein Structure and Design by Genetic Experiments.
Rollins, Nathanael Jedidiah Reodica.

Protein Structure and Design by Genetic Experiments. - Ann Arbor : ProQuest Dissertations & Theses, 2020 - 186 p.

Source: Dissertations Abstracts International, Volume: 82-06, Section: B.

Thesis (Ph.D.)--Harvard University, 2020.

This item must not be sold to any third party vendors.

Gene sequences refined by natural selection contain evidence of the interactions essential for function. By modeling natural sequences, we can now solve protein and RNA 3D folds and design new molecules and systems. Now we are also beginning to create genetic data in the lab faster than nature does, and we can explore genetic sequences and phenotypes nature hasn't. How can laboratory selection be leveraged to discover underlying biology and design new genes?Here we show that the 3D folds of proteins and RNAs can be solved ab initio using deep mutation scans. We also design small, targeted mutation scans to solve protein structures efficiently. Second, we solve the structure of human vitamin K epoxide reductase with natural sequences and use mutation scans to dissect the mechanisms of drug-interfering mutants. Lastly, we determine mechanisms of thioesterase specificity and design enhanced enzymes for production of fuels and plastics using laboratory recombination. As DNA technology continues to accelerate, we propose such methods will in turn accelerate basic biology and biological design.

ISBN: 9798698539834Subjects--Topical Terms:

517296
Molecular biology.
Subjects--Index Terms:

High-throughput mutation scans

Protein Structure and Design by Genetic Experiments.
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100 1 $a Rollins, Nathanael Jedidiah Reodica. $0 (orcid)0000-0002-8037-6045 $3 3556803
245 1 0 $a Protein Structure and Design by Genetic Experiments.
260 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2020
300 $a 186 p.
500 $a Source: Dissertations Abstracts International, Volume: 82-06, Section: B.
500 $a Includes supplementary digital materials.
500 $a Advisor: Marks, Debora S.;Silver, Pamela A.
502 $a Thesis (Ph.D.)--Harvard University, 2020.
506 $a This item must not be sold to any third party vendors.
520 $a Gene sequences refined by natural selection contain evidence of the interactions essential for function. By modeling natural sequences, we can now solve protein and RNA 3D folds and design new molecules and systems. Now we are also beginning to create genetic data in the lab faster than nature does, and we can explore genetic sequences and phenotypes nature hasn't. How can laboratory selection be leveraged to discover underlying biology and design new genes?Here we show that the 3D folds of proteins and RNAs can be solved ab initio using deep mutation scans. We also design small, targeted mutation scans to solve protein structures efficiently. Second, we solve the structure of human vitamin K epoxide reductase with natural sequences and use mutation scans to dissect the mechanisms of drug-interfering mutants. Lastly, we determine mechanisms of thioesterase specificity and design enhanced enzymes for production of fuels and plastics using laboratory recombination. As DNA technology continues to accelerate, we propose such methods will in turn accelerate basic biology and biological design.
590 $a School code: 0084.
650 4 $a Molecular biology. $3 517296
650 4 $a Systematic biology. $3 3173492
650 4 $a Evolution & development. $3 3172418
650 4 $a Genetics. $3 530508
653 $a High-throughput mutation scans
653 $a Probabilistic models
653 $a Protein design
653 $a Protein structure
690 $a 0307
690 $a 0423
690 $a 0412
690 $a 0369
710 2 $a Harvard University. $b Biology, Molecular and Cellular. $3 2093132
773 0 $t Dissertations Abstracts International $g 82-06B.
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791 $a Ph.D.
792 $a 2020
793 $a English
856 4 0 $u https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28151433