東華大學圖書館 |

Language: English

Help

回圖書館首頁

手機版館藏查詢

Back

Switch To: Labeled | MARC Mode | ISBD

Statistical knowledge-based approach...

Kuznetsov, Igor Borisovich.

Linked to FindBook

Google Book

Amazon

博客來

Statistical knowledge-based approach to sequence/structure relationships in proteins.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Statistical knowledge-based approach to sequence/structure relationships in proteins./
Author:	Kuznetsov, Igor Borisovich.
Description:	252 p.
Notes:	Source: Dissertation Abstracts International, Volume: 64-02, Section: B, page: 0584.
Contained By:	Dissertation Abstracts International64-02B.
Subject:	Biophysics, Medical. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3079383

Statistical knowledge-based approach to sequence/structure relationships in proteins.
Kuznetsov, Igor Borisovich.

Statistical knowledge-based approach to sequence/structure relationships in proteins. - 252 p.

Source: Dissertation Abstracts International, Volume: 64-02, Section: B, page: 0584.

Thesis (Ph.D.)--Mount Sinai School of Medicine of New York University, 2003.

In this work we perform a statistical analysis of experimentally solved protein structures to study correlations between the properties of amino acid sequence and its final native structure, and address the following problems. (1) We study a phenomenon of conformational variability observed in the prion protein (PrP). A structural conversion of a normal, mostly α-helical cellular PrP into a pathogenic β-sheet-rich conformation causes fatal neurodegenerative diseases. First, we analyze the properties of structurally ambivalent sequence fragments (SASFs). Each SASF adopts two different conformations in two different proteins. Second, the data derived from the analysis of SASFs are used to study the properties of the prion protein, and gain insights into possible mechanisms of structural conversion. We show that the prion protein contains at least two sequence fragments with highly unusual intrinsic propensities, PrP(114–125) and helix B. These fragments are the primary candidates for conversion into β-sheet conformation and potential oligomerization sites. We also show that most PrP mutations associated with neurodegenerative disorders significantly increase the degree of local conformational variability. (2) We present a novel method designed to analyze and optimize the discriminative ability of knowledge-based potentials of mean force with respect to the 20 residue types. The method is based on the preference of amino acids for specific types of protein environment, and uses a virtual mutagenesis experiment to estimate how much information a given potential can provide about environments of each amino acid type. This method also allows one to obtain potential-specific matrices of distances between the amino acid types. The weighted combinations of these potential-specific matrices are optimized in order to obtain an amino acid exchange matrix which performs optimally in sequence alignment. (3) We perform a comparative analysis of correlations between global topological features of protein structure, sequence properties and folding rate in small single domain proteins with two-state kinetics. A novel correlation between the rate of folding and average intrinsic structural propensity of amino acid sequence is reported.Subjects--Topical Terms:

1017681
Biophysics, Medical.

Statistical knowledge-based approach to sequence/structure relationships in proteins.
LDR:03215nmm 2200277 4500 001 1857532
005 20040816072813.5
008 130614s2003 eng d
035 $a (UnM)AAI3079383
035 $a AAI3079383
040 $a UnM $c UnM
100 1 $a Kuznetsov, Igor Borisovich. $3 1945249
245 1 0 $a Statistical knowledge-based approach to sequence/structure relationships in proteins.
300 $a 252 p.
500 $a Source: Dissertation Abstracts International, Volume: 64-02, Section: B, page: 0584.
500 $a Adviser: Shalom Rackovsky.
502 $a Thesis (Ph.D.)--Mount Sinai School of Medicine of New York University, 2003.
520 $a In this work we perform a statistical analysis of experimentally solved protein structures to study correlations between the properties of amino acid sequence and its final native structure, and address the following problems. (1) We study a phenomenon of conformational variability observed in the prion protein (PrP). A structural conversion of a normal, mostly α-helical cellular PrP into a pathogenic β-sheet-rich conformation causes fatal neurodegenerative diseases. First, we analyze the properties of structurally ambivalent sequence fragments (SASFs). Each SASF adopts two different conformations in two different proteins. Second, the data derived from the analysis of SASFs are used to study the properties of the prion protein, and gain insights into possible mechanisms of structural conversion. We show that the prion protein contains at least two sequence fragments with highly unusual intrinsic propensities, PrP(114–125) and helix B. These fragments are the primary candidates for conversion into β-sheet conformation and potential oligomerization sites. We also show that most PrP mutations associated with neurodegenerative disorders significantly increase the degree of local conformational variability. (2) We present a novel method designed to analyze and optimize the discriminative ability of knowledge-based potentials of mean force with respect to the 20 residue types. The method is based on the preference of amino acids for specific types of protein environment, and uses a virtual mutagenesis experiment to estimate how much information a given potential can provide about environments of each amino acid type. This method also allows one to obtain potential-specific matrices of distances between the amino acid types. The weighted combinations of these potential-specific matrices are optimized in order to obtain an amino acid exchange matrix which performs optimally in sequence alignment. (3) We perform a comparative analysis of correlations between global topological features of protein structure, sequence properties and folding rate in small single domain proteins with two-state kinetics. A novel correlation between the rate of folding and average intrinsic structural propensity of amino acid sequence is reported.
590 $a School code: 1353.
650 4 $a Biophysics, Medical. $3 1017681
650 4 $a Biology, Molecular. $3 1017719
650 4 $a Biology, Biostatistics. $3 1018416
690 $a 0760
690 $a 0307
690 $a 0308
710 2 0 $a Mount Sinai School of Medicine of New York University. $3 1025278
773 0 $t Dissertation Abstracts International $g 64-02B.
790 1 0 $a Rackovsky, Shalom, $e advisor
790 $a 1353
791 $a Ph.D.
792 $a 2003
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3079383