Development of methods for docking and designing small molecules within the Rosetta code framework

Structure-based drug design is a key challenge for pharmaceutical chemists. By studying the structure of proteins bound to natural substrates, researchers can design small molecules which they predict will bind in a similar fashion. Ligand docking software such as RosettaLigand plays a key role in s...

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Main Author:	Lemmon, Gordon Howard
Other Authors:	David Tabb
Format:	Others
Language:	en
Published:	VANDERBILT 2012
Subjects:	Chemical and Physical Biology
Online Access:	http://etd.library.vanderbilt.edu/available/etd-10152012-130148/

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spelling	ndltd-VANDERBILT-oai-VANDERBILTETD-etd-10152012-1301482013-01-08T17:17:01Z Development of methods for docking and designing small molecules within the Rosetta code framework Lemmon, Gordon Howard Chemical and Physical Biology Structure-based drug design is a key challenge for pharmaceutical chemists. By studying the structure of proteins bound to natural substrates, researchers can design small molecules which they predict will bind in a similar fashion. Ligand docking software such as RosettaLigand plays a key role in structure-based drug design by predicting how a small molecule and a protein will interact. In this body of research I present improvements to the RosettaLigand docking algorithm. I first demonstrate a strategy for achieving accurate predictions of HIV-1 protease/protease inhibitor binding affinity. Next I present a tutorial for using a new version of RosettaLigand docking code which I wrote. This new version allows simultaneous docking of multiple ligands, docking with interface design, and uses an XML-script interface. The XML interface allows fully customizable ligand docking protocols. Finally I demonstrate simultaneous docking of waters along with small molecule inhibitors within protein interfaces. Water docking improves Rosettas ability to predict the structure of the protein/inhibitor interface. David Tabb Brian Bachmann Jarrod Smith Richard D'Aquila VANDERBILT 2012-10-15 text application/pdf http://etd.library.vanderbilt.edu/available/etd-10152012-130148/ http://etd.library.vanderbilt.edu/available/etd-10152012-130148/ en unrestricted I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report.
collection	NDLTD
language	en
format	Others
sources	NDLTD
topic	Chemical and Physical Biology
spellingShingle	Chemical and Physical Biology Lemmon, Gordon Howard Development of methods for docking and designing small molecules within the Rosetta code framework
description	Structure-based drug design is a key challenge for pharmaceutical chemists. By studying the structure of proteins bound to natural substrates, researchers can design small molecules which they predict will bind in a similar fashion. Ligand docking software such as RosettaLigand plays a key role in structure-based drug design by predicting how a small molecule and a protein will interact. In this body of research I present improvements to the RosettaLigand docking algorithm. I first demonstrate a strategy for achieving accurate predictions of HIV-1 protease/protease inhibitor binding affinity. Next I present a tutorial for using a new version of RosettaLigand docking code which I wrote. This new version allows simultaneous docking of multiple ligands, docking with interface design, and uses an XML-script interface. The XML interface allows fully customizable ligand docking protocols. Finally I demonstrate simultaneous docking of waters along with small molecule inhibitors within protein interfaces. Water docking improves Rosettas ability to predict the structure of the protein/inhibitor interface.
author2	David Tabb
author_facet	David Tabb Lemmon, Gordon Howard
author	Lemmon, Gordon Howard
author_sort	Lemmon, Gordon Howard
title	Development of methods for docking and designing small molecules within the Rosetta code framework
title_short	Development of methods for docking and designing small molecules within the Rosetta code framework
title_full	Development of methods for docking and designing small molecules within the Rosetta code framework
title_fullStr	Development of methods for docking and designing small molecules within the Rosetta code framework
title_full_unstemmed	Development of methods for docking and designing small molecules within the Rosetta code framework
title_sort	development of methods for docking and designing small molecules within the rosetta code framework
publisher	VANDERBILT
publishDate	2012
url	http://etd.library.vanderbilt.edu/available/etd-10152012-130148/
work_keys_str_mv	AT lemmongordonhoward developmentofmethodsfordockinganddesigningsmallmoleculeswithintherosettacodeframework
_version_	1716570601060040704

Development of methods for docking and designing small molecules within the Rosetta code framework

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