Abstract/Details

Computational and theoretical studies of globular proteins


2005 2005

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Abstract (summary)

Protein crystallization is often achieved in experiment through a trial and error approach. To date, there exists a dearth of theoretical understanding of the initial conditions necessary to promote crystallization. While a better understanding of crystallization will help to create good crystals suitable for structure analysis, it will also allow us to prevent the onset of certain diseases. The core of this thesis is to model and, ultimately, understand the phase behavior of protein particles in solution. Toward this goal, we calculate the fluid-fluid coexistence curve in the vicinity of the metastable critical point of the modified Lennard-Jones potential, where it has been shown that nucleation is increased by many orders of magnitude. We use finite-size scaling techniques and grand canonical Monte Carlo simulation methods. This has allowed us to pinpoint the critical point and subcritical region with high accuracy in spite of the critical fluctuations that hinder sampling using other Monte Carlo techniques. We also attempt to model the phase behavior of the γ-crystallins, mutations of which have been linked to genetic cataracts. The complete phase behavior of the square well potential at the ranges of attraction λ = 1.15 and λ = 1.25 is calculated and compared with that of the γII-crystallin. The role of solvent is also important in the crystallization process and affects the phase behavior of proteins in solution. We study a model that accounts for the contribution of the solvent free-energy to the free-energy of globular proteins. This model allows us to model phase behavior that includes solvent.

Indexing (details)


Subject
Condensation;
Biochemistry
Classification
0611: Condensation
0487: Biochemistry
Identifier / keyword
Pure sciences; Crystallins-gamma; Crystallization; Globular proteins; Lennard-Jones potential; Protein crystallization
Title
Computational and theoretical studies of globular proteins
Author
Pagan, Daniel L.
Number of pages
153
Publication year
2005
Degree date
2005
School code
0105
Source
DAI-B 66/04, Dissertation Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
ISBN
0542086921, 9780542086922
Advisor
Gunton, James D.
University/institution
Lehigh University
University location
United States -- Pennsylvania
Degree
Ph.D.
Source type
Dissertations & Theses
Language
English
Document type
Dissertation/Thesis
Dissertation/thesis number
3172195
ProQuest document ID
304996007
Copyright
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
http://search.proquest.com/docview/304996007
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