Molecular Dynamics Studies of Interfacial Effects on Protein Conformation
Braun, Rosemary Irene
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Permalink
https://hdl.handle.net/2142/32097
Description
Title
Molecular Dynamics Studies of Interfacial Effects on Protein Conformation
Author(s)
Braun, Rosemary Irene
Issue Date
2004-10
Director of Research (if dissertation) or Advisor (if thesis)
Schulten, Klaus J.
Department of Study
Physics
Discipline
Physics
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Molecular dynamics
lipid bilayer membrane
molecular dynamics (MD) simulations
Language
en
Abstract
A better understanding of life at a microscopic level permits the formulation of better drugs, the
imitation of biological processes for technological applications, and the prediction of the impact
of pathogenic substances. At the heart of biological molecular processes lies the interaction of
polypeptides with solvent and lipid environments; technological applications rely on the interaction
of polypeptides with inorganic substrates. Molecular dynamics (MD) simulations provide a means
by which these interactions may be examined in atomic-level detail, offering increasing speed and
accuracy, as well as applicability to progressively larger system sizes and longer simulation times.
This thesis describes the application of molecular dynamics simulation technique to several systems
in which interfacial effects on protein conformation are of interest.
In the first chapter, a detailed description of MD simulations is presented. The physical basis
for the methodology is discussed, followed by a description of the algorithms implemented to carry
out the simulations. The chapter concludes with a description of the techniques used to initialize,
carry out, and analyze simulations.
The second chapter describes the application of MD simulation to a system of biological interest
[6]. It is well-known that a lipid bilayer membrane provides an impermeable barrier around
living cells, and that transmembrane proteins, often comprising several non-bonded subunits, form
pores and channels in the membrane to permit the passage of resources and waste as well as regulate
osmotic pressure. It is still unclear, however, how these proteins are incorporated into the
membrane and how complex transmembrane structures are formed. A model system, consisting of
a transmembrane helix dimer in a spherical aggregate of lipids (micelle) is examined and compared
to a mutant system by way of MD simulation; the spontaneous aggregation of lipids into a micelle
surrounding the protein from an initially random configuration is also described, and compared to
a theoretical diffusion model. The third chapter describes the application of MD simulations to a system of technological
interest: a gold-binding protein in contact with a gold crystal surface [7]. The biological control of
inorganic crystal formation, morphology and assembly is of interest to biologists and biotechnologists
studying hard tissue growth and regeneration, as well as to material scientists using biomimetic
approaches for control of inorganic material fabrication and assembly. Structure predictions for gold
binding protein sequences, originally selected by combinatorial techniques, are presented. Molecular
dynamics simulations were carried out using solvated polypeptides at the gold surface, and
the dynamics of the binding process and the effects of surface topography on binding affinity are
described.
Lastly, in an appendix, a method for determining the potential of mean force from a steered
molecular dynamics simulation is presented [8].
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