자료유형  

 학위논문

Control Number  

0015492191

International Standard Book Number  

9781085714648

Dewey Decimal Classification Number  

610

Main Entry-Personal Name  

Pederson, Eric.

Publication, Distribution, etc. (Imprint  

[Sl] : University of Washington, 2019

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2019

Physical Description  

147 p

General Note  

Source: Dissertations Abstracts International, Volume: 81-03, Section: B.

General Note  

Advisor: Interlandi, Gianluca.

Dissertation Note  

Thesis (Ph.D.)--University of Washington, 2019.

Restrictions on Access Note  

This item must not be sold to any third party vendors.

Restrictions on Access Note  

This item must not be added to any third party search indexes.

Summary, Etc.  

요약Upon vascular injury, fibrin is converted from fibrinogen and polymerizes to form long protofibrils. Protofibrils laterally aggregate via the 慣C domain to form fibrin fibers, which bind to platelets and form a clot. Inflammation recruits pro-inflammatory neutrophils to the site of injury, which produce HOCl via myeloperoxidase. Inflammation is associated with abnormal clot morphologies, which can lead to thrombosis and bleeding. Fibrin Met476, located in the 慣C domain, oxidizes upon exposure to myeloperoxidase-derived HOCl, which subsequently disrupts lateral aggregation and produces abnormal clots. The mechanism by which oxidation affects 慣C domain structure, dynamics and self-association was investigated by enhanced-sampling molecular dynamics techniques and free energy calculations. Replica exchange molecular dynamics simulations with an implicit solvent were used to efficiently sample 慣C-domain dimer conformations. Low-energy conformers were identified from the free energy landscape minima and were used for free energy calculations after equilibra- tion in explicit solvent. Using this method, I propose the hydrophobic core model of 慣C polymerization, which states that Met476 is a docking spot for 慣C polymerization.

Subject Added Entry-Topical Term  

Biochemistry

Subject Added Entry-Topical Term  

Biophysics

Subject Added Entry-Topical Term  

Bioengineering

Added Entry-Corporate Name  

University of Washington Bioengineering

Host Item Entry  

Dissertations Abstracts International. 81-03B.

Host Item Entry  

Dissertation Abstract International

Electronic Location and Access  

로그인을 한후 보실 수 있는 자료입니다.

Control Number  

joongbu:565582