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Attractive Patchy Protein Interactions : Understanding of protein dimerization

Li, Weimin LU (2016)
Abstract (Swedish)
Protein interactions are important in understanding various
protein relevant cellular and technological processes.
This is a challenging task due to the intrinsically irregular shape and
inhomogeneous surface distribution of
neutral, charged, hydrophobic amino acid residues. This results in
more or less anisotropic interactions depending on external parameters such as
salt and pH. However, a deeper understanding of these complex
interactions is essential in order to
understand the behavior of proteins in solution and
protein phase diagrams. The aim of this work was to gain a deeper understanding
of protein attractions, in particular, anisotropic protein attractions.
We have for this... (More)
Protein interactions are important in understanding various
protein relevant cellular and technological processes.
This is a challenging task due to the intrinsically irregular shape and
inhomogeneous surface distribution of
neutral, charged, hydrophobic amino acid residues. This results in
more or less anisotropic interactions depending on external parameters such as
salt and pH. However, a deeper understanding of these complex
interactions is essential in order to
understand the behavior of proteins in solution and
protein phase diagrams. The aim of this work was to gain a deeper understanding
of protein attractions, in particular, anisotropic protein attractions.
We have for this reason
studied the protein lactoferrin. We have found and characterized a
highly directional attraction which combined with Monte Carlo (MC) simulations
show the mechanism as
a highly directional short-ranged electrostatic attraction, originated from few
ionizable amino acids.
This gives rise to a non-monotonic dependence
of the second virial coefficient, $B_2$, with ionic strength
both in scattering experiments and
MC simulations, in qualitative agreement.
Further, we show how the directional attraction is effectively behaving as an attractive patch
that leads to dimerization of lactoferrin under patch attractive conditions.
The phase diagram is also determined under patch conditions where
new phases are discovered using cryo-transmission electron microscope.
Finally, we explored protein capacitance obtained both
from titration experiments and MC computer calculations
which is related to charge regulation attraction. (Less)
Abstract
Protein interactions are important in understanding various
protein relevant cellular and technological processes.
This is a challenging task due to the intrinsically irregular shape and
inhomogeneous surface distribution of
neutral, charged, hydrophobic amino acid residues. This results in
more or less anisotropic interactions depending on external parameters such as
salt and pH. However, a deeper understanding of these complex
interactions is essential in order to
understand the behavior of proteins in solution and
protein phase diagrams. The aim of this work was to gain a deeper understanding
of protein attractions, in particular, anisotropic protein attractions.
We have for this... (More)
Protein interactions are important in understanding various
protein relevant cellular and technological processes.
This is a challenging task due to the intrinsically irregular shape and
inhomogeneous surface distribution of
neutral, charged, hydrophobic amino acid residues. This results in
more or less anisotropic interactions depending on external parameters such as
salt and pH. However, a deeper understanding of these complex
interactions is essential in order to
understand the behavior of proteins in solution and
protein phase diagrams. The aim of this work was to gain a deeper understanding
of protein attractions, in particular, anisotropic protein attractions.
We have for this reason
studied the protein lactoferrin. We have found and characterized a
highly directional attraction which combined with Monte Carlo (MC) simulations
show the mechanism as
a highly directional short-ranged electrostatic attraction, originated from few
ionizable amino acids.
This gives rise to a non-monotonic dependence
of the second virial coefficient, $B_2$, with ionic strength
both in scattering experiments and
MC simulations, in qualitative agreement.
Further, we show how the directional attraction is effectively behaving as an attractive patch
that leads to dimerization of lactoferrin under patch attractive conditions.
The phase diagram is also determined under patch conditions where
new phases are discovered using cryo-transmission electron microscope.
Finally, we explored protein capacitance obtained both
from titration experiments and MC computer calculations
which is related to charge regulation attraction. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Professor Lenhoff, Abraham M., University of Delaware, Newark, USA
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Patchy Attractions, Protein Interactions
pages
106 pages
publisher
Division of Physical Chemistry, Faculty of Science, Lund University
defense location
Center for chemistry and chemical engineering, lecture hall B, Naturvetarvägen 14, Lund
defense date
2016-09-16 9:30
ISBN
978-91-7422-466-5
language
English
LU publication?
yes
id
d03374e8-1e65-49c0-8f7e-20e4d0475150
date added to LUP
2016-08-22 10:45:30
date last changed
2016-09-19 08:45:20
@phdthesis{d03374e8-1e65-49c0-8f7e-20e4d0475150,
  abstract     = {Protein interactions are important in understanding various <br/>protein relevant cellular and technological processes.<br/>This is a challenging task due to the intrinsically irregular shape and <br/>inhomogeneous surface distribution of <br/>neutral, charged, hydrophobic amino acid residues. This results in<br/>more or less anisotropic interactions depending on external parameters such as<br/>salt and pH. However, a deeper understanding of these complex<br/>interactions is essential in order to <br/>understand the behavior of proteins in solution and <br/>protein phase diagrams. The aim of this work was to gain a deeper understanding <br/>of protein attractions, in particular, anisotropic protein attractions. <br/>We have for this reason<br/>studied the protein lactoferrin. We have found and characterized a<br/>highly directional attraction which combined with Monte Carlo (MC) simulations <br/>show the mechanism as<br/>a highly directional short-ranged electrostatic attraction, originated from few <br/>ionizable amino acids. <br/>This gives rise to a non-monotonic dependence <br/>of the second virial coefficient, $B_2$, with ionic strength<br/>both in scattering experiments and <br/>MC simulations, in qualitative agreement. <br/>Further, we show how the directional attraction is effectively behaving as an attractive patch<br/>that leads to dimerization of lactoferrin under patch attractive conditions.<br/>The phase diagram is also determined under patch conditions where <br/>new phases are discovered using cryo-transmission electron microscope.<br/>Finally, we explored protein capacitance obtained both <br/>from titration experiments and MC computer calculations<br/>which is related to charge regulation attraction.},
  author       = {Li, Weimin},
  isbn         = {978-91-7422-466-5},
  keyword      = {Patchy Attractions,Protein Interactions},
  language     = {eng},
  pages        = {106},
  publisher    = {Division of Physical Chemistry, Faculty of Science, Lund University},
  school       = {Lund University},
  title        = {Attractive Patchy Protein Interactions : Understanding of protein dimerization},
  year         = {2016},
}