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Author Fischer, Kael Frank
Title Locating autonomous folding units in proteins
book jacket
Descript 110 p
Note Source: Dissertation Abstracts International, Volume: 63-09, Section: B, page: 4084
Chair: Susan Marqusee
Thesis (Ph.D.)--University of California, Berkeley, 2002
Understanding the mechanisms of action of proteins is complicated by the apparent all-or-none nature of protein structure. The characteristic cooperativity of proteins obscures attempts to parse the many interactions in a structure into the smaller networks that directly give rise to a particular property. Dissection of proteins is one way to distinguish between protein regions that encode their structure locally and those that rely on more remote tertiary contexts. Autonomous Folding Units (AFUs) that retain their structure when excised from larger proteins can provide models for examination of parts of a protein's structure and some of the protein's functions in a simpler context. This work presents the motivation, development and application of a system to locate AFUs using the high-resolution structure of a complete domain. The Rapid Autonomous Fragment Test (RAFT) is described and tested with a collection of previously characterized fragments, showing that RAFT is able to distinguish between autonomous segments and non-autonomous segments of domains. Additional fragments are designed using RAFT and they are characterized and compared along with related fragments designed without the use of RAFT, the RAFT score is shown to be correlated with the extent to which these fragments dissociate to monomeric subunits (with no apparent loss of structure) and hence their autonomy. The RAFT score is shown to be at least as good at locating structural autonomy as a related score based on more precise energetic terms. Lastly RAFT was used to locate autonomous representatives of 30 small topologies; 29 of the 30 topologies were found to have representatives that are suitable targets for protein design. RAFT is a robust method for location of AFUs, and is available to the biophysics community as tool for assessing structural autonomy in proteins
School code: 0028
Host Item Dissertation Abstracts International 63-09B
Subject Biophysics, General
Alt Author University of California, Berkeley
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