Find results with:

Add another field

Search by date

to

Searching collections:

Dartmouth Dissertations

Add or remove collections

Home Dartmouth Dissertations Page 1

Reference URL

To link to the entire object, paste this link in email, IM or document

To embed the entire object, paste this HTML in website

To link to this page, paste this link in email, IM or document

To embed this page, paste this HTML in website

Optimization algorithms for site-directed protein recombination experiment planning.

you wish to report:

Your comment:

Your Name:

Submit

Cancel

...

Back to top

Powered by CONTENTdm®

Call No.	Ph.D. 2010 c.2
Author	Zheng, Wei.
Title	Optimization algorithms for site-directed protein recombination experiment planning.
Date	2010
Abstract	Site-directed protein recombination produces improved and novel protein variants by recombining sequence fragments from parent proteins. The resulting hybrids accumulate multiple mutations that have been evolutionarily accepted together. Subsequent screening or selection identifies hybrids with desirable characteristics. In order to increase the "hit rate" of good variants, this thesis develops experiment planning algorithms to optimize protein recombination experiments. First, to improve the frequency of generating novel hybrids, a metric is developed to assess the diversity among hybrids and parent proteins. Dynamic programming algorithms are then created to optimize the selection of breakpoint locations according to this metric. Second, the trade-off between diversity and stability in recombination experiment planning is studied, recognizing that diversity requires changes from parent proteins, which may also disrupt important residue interactions necessary for protein stability. Accordingly, methods based on dynamic programming are developed to provide combined optimization of diversity and stability, finding optimal breakpoints such that no other experiment plan has better performance in both aspects simultaneously. Third, in order to support protein recombination with heterogeneous structures and focus on functionally important regions, a general framework for protein fragment swapping is developed. Differentiating source and target parents, and swappable regions within them, fragment swapping enables asymmetric, selective site-directed recombination. Two applications of protein fragment swapping are studied. In order to generate hybrids inheriting functionalities from both source and target proteins by fragment swapping, a method based on integer programming selects optimal swapping fragments to maximize the predicted stability and activity of hybrids in the resulting library. In another application, human source protein fragments are swapped into therapeutic exogenous target protein to minimize the occurrence of peptides that trigger immune response. A dynamic programming method is developed to optimize fragment selection for both humanity and functionality, resulting in therapeutically active variants with decreased immunogenicity.
Description	xiii, 136 leaves : col. ill. ; 28 cm.
Format	application/pdf
Advisor	Bailey-Kellogg, Chris, Balkcom, Devin, Fleischer, Lisa K., Griswold, Karl E.
Subject	Proteins -- Structure -- Mathematical models. Recombinant proteins -- Mathematical models. Mathematical optimization -- Data processing. Dynamic programming. Protein engineering.
College	Dartmouth College. Dept. of Computer Science.
Issuing Body	Dartmouth Dissertations are made available through the Dartmouth Digital Library.
Degree	Thesis (Ph.D.)--Dartmouth College.
Copyright	All rights reserved. No part of this book may be reproduced in any form by any electronic or mechanical means without permission in writing from the author.
DOI	http://dx.doi.org/10.1349/ddlp.372

Title	Page 1
Format	application/pdf
Issuing Body	Dartmouth Dissertations are made available through the Dartmouth Digital Library.
Degree	Thesis (Ph.D.)--Dartmouth College.
Full Text	Optimization Algorithms for Site-directed Protein Recombination Experiment Planning A Thesis Submitted to the Faculty in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Computer Science by Wei Zheng DARTMOUTH COLLEGE Hanover, New Hampshire June 2010 Examining Committee: (chair) Chris Bailey-Kellogg Devin Balkcom Lisa K. Fleischer Karl E. Griswold Brian W. Pogue, PhD. Dean of Graduate Studies

Find results with:

Searching collections:

Home Dartmouth Dissertations Page 1

Optimization algorithms for site-directed protein recombination experiment planning.

Object Description

Description

Optimization algorithms for site-directed protein...

Optimization algorithms for site-directed protein...

	All
	Pages Enter page numbers or page ranges separated by commas. For example: 1,3,5-12