Ab initio Prediction of the Conformation of Solvated and Adsorbed Proteins
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Date
2008Author
Mijajlovic, Milan
Metadata
Abstract
Proteins are among the most important groups of biomolecules, with their
biological functions ranging from structural elements to signal transducers between
cells. Apart from their biological role, phenomena related to protein behaviour in
solutions and at solid interfaces can find a broad range of engineering applications
such as in biomedical implants, scaffolds for artificial tissues, bioseparations,
biomineralization and biosensors. For both biological and engineering applications,
the functionality of a protein is directly related to its three-dimensional structure (i.e.
conformation). Methods such as homology and threading that depend on a large
database of existing experimental knowledge are the most popular means of
predicting the conformation of proteins in their native environment. Lack of
sufficient experimentally-derived information for non-native environments such as
general solutions and solid interfaces prevents these knowledge-based methods being
used for such environments. Resort must, instead, be made to so-called ab initio
methods that rely upon knowledge of the primary sequence of the protein, its
environment, and the physics of the interatomic interactions. The development of
such methods for non-native environments is in its infancy – this thesis reports on the
development of such a method and its application to proteins in water and at
gas/solid and water/solid interfaces. After introducing the approach used – which is
based on evolutionary algorithms (EAs) – we first report a study of polyalanine
adsorbed at a gas/solid interface in which a switching behaviour is observed that, to
our knowledge, has never been reported before. The next section reports work that
shows the combination of the Langevin dipole (LD) solvent method with the Amber
potential energy (PE) model is able to yield solvation energies comparable to those
of more sophisticated methods at a fraction of the cost, and that the LD method is
able to capture effects that arise from inhomogenities in the water structure such as
H-bond bridges. The third section reports a study that shows that EA performance
and optimal control parameters vary substantially with the PE model. The first three
parts form the basis of the last part of the thesis, which reports pioneering work on
predicting ab initio the conformation of proteins in solutions and at water/solid
interfaces.