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Statistical, Computationally Assisted Design Strategy :Development of the method and applications to designing proteins and a non-biological foldamer

Record Type:	Electronic resources : Monograph/item
Title/Author:	Statistical, Computationally Assisted Design Strategy :
Reminder of title:	Development of the method and applications to designing proteins and a non-biological foldamer
Author:	Fu, Xiaoran.
Description:	294 p.
Notes:	Source: Dissertation Abstracts International, Volume: 65-03, Section: B, page: 1339.
Notes:	Supervisor: Jeffery G. Saven.
Contained By:	Dissertation Abstracts International65-03B.
Subject:	Chemistry, Physical.
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3125822
ISBN:	0496731114

Statistical, Computationally Assisted Design Strategy :Development of the method and applications to designing proteins and a non-biological foldamer
Fu, Xiaoran.

Statistical, Computationally Assisted Design Strategy :Development of the method and applications to designing proteins and a non-biological foldamer [electronic resource] - 294 p.

Source: Dissertation Abstracts International, Volume: 65-03, Section: B, page: 1339.

Thesis (Ph.D.)--University of Pennsylvania, 2004.

Rational and computational protein design have been studied extensively during the past two decades. Some rational design studies have been able to find desirable sequences using empirical knowledge. However, computationally guided protein design may explain quantitatively some features of protein folding that are inaccessible to experiments. Deterministic and stochastic protein design algorithms have been developed and implemented by a number of different research groups. Extensive computation time is required in most of the design algorithms. Herein, a statistical design method, SCADS (Statistical, Computationally Assisted Design Strategy) is presented, yielding a fast method for design and for identifying sequence properties. A symmetry assumption is implemented in this thesis to study highly symmetrical protein structures, which are prevalent in nature. The computational time with implementing the symmetry assumption can be as short as 1/M2 that without the symmetry assumption, where M is the symmetry order. SCADS is then applied to study several symmetrical structures, including non-natural de novo structures. A fast scan method is developed based on SCADS to locate one or a few "good" backbone tertiary structures from an ensemble of possible de novo structures. A negative design concept is introduced in designing a dimeric membrane protein using the fast scan method. SCADS is applied to identifying potential mutations in native proteins (albumin-binding domain GA module, 1PRB) to study the effect of mutations on both the folding thermodynamic and kinetic properties. The method is also applied to designing a combinatorial library of a de novo designed protein---alpha3D. The potential mutations of a subtilisin propeptide are identified to stabilize the unstructured protein. As an extension of the protein design study, SCADS is adapted and applied to designing a non-biological foldamer with slight modifications of the algorithm. Foldamer sequences with potentially enhanced binding affinity and binding specificity for a small chiral ligand molecule are designed using the modified SCADS methodology.

ISBN: 0496731114Subjects--Topical Terms:

226924
Chemistry, Physical.

Statistical, Computationally Assisted Design Strategy :Development of the method and applications to designing proteins and a non-biological foldamer
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