Anisotropic Protein Interactions in Salt Solutions and at Interfaces: Coarse Grained Modeling

Anil Kurut Sabanoglu

Forskningsoutput: AvhandlingDoktorsavhandling (sammanläggning)

79 Nedladdningar (Pure)

Sammanfattning

Popular Abstract in English
Proteins are molecular machines of the human body which regulate all life sustaining processes such as energy production, communication, transport of essential molecules, defense against microbes, etc. They are built by small molecular units called amino acids, bound together like pearls on a necklace. Each amino acid consists of a common part and a unique side chain. The former makes up the backbone of a protein chain and the latter determines the nature of the amino acid. There are 22 kinds of amino acid side chains which provide an enormous diversity to the protein chains. The amino acid side chains can have a water- (polar) or oil-like (hydrophobic) nature. Some polar amino acids may bear a positive or negative charge depending on the environmental conditions such as acidity and salt concentration. It is a well-known phenomenon that water tends to separate from oil. This also holds for an oil-like, hydrophobic amino acid where water tends to push these amino acids together to avoid contact with them. Due to this tendency, the protein chains fold into a globular shape so that most of the hydrophobic amino acids are located in the protein interior and the polar amino acids are on the surface. However, some proteins that lack hydrophobic amino acids do not fold into a globular shape and behave as flexible chains. These proteins are called intrinsically disordered proteins.
The nature of protein interactions is determined by the distribution of charged and hydrophobic amino acids on the surface, in case of globular proteins, or in the chain, in case of disordered proteins. The segregation of positive amino acids from the negative ones results in anisotropic interactions which resemble the interactions of two magnets where opposite poles abstract and the similar ones repel each other. Thus, the nature of anisotropic interactions depends on the orientations of the proteins. These interactions can also originate from clustering of hydrophobic amino acids on protein surfaces, which creates sticky surface patches.
In this thesis, we have studied the effect of hydrophobic and charge patchiness of protein surfaces on the protein-protein and protein-surface interactions in salt solutions. We used Monte Carlo simulations to mimic protein behaviors with the help of computers and played around with the acidity and salt concentration of the protein solutions to determine their impact. We have developed system specific protein models which represent proteins by collections of interacting spheres. In the model development, we used a coarse graining approach where we have only considered the details of proteins that are essential for the specific study.
We have shown that the hydrophobic and charge patchiness on a protein surface can be altered by binding of charged salt species on the protein surface – called the Hofmeister ion effect. Under correct solution acidity, the charge residues can adapt a charged or neutral state to maximize attraction with opposite charges or to minimize repulsion with similar charges. This phenomenon is called charge regulation which can also alter the charge patchiness of the protein surfaces. The resulting complex patch interactions may reinforce specific protein orientations, and may facilitate protein associations into functional machines.
Originalspråkengelska
KvalifikationDoktor
Tilldelande institution
  • Teoretisk kemi
Handledare
  • Lund, Mikael, handledare
Tilldelningsdatum2014 sep. 19
Förlag
ISBN (tryckt)978-91-7422-365-1
StatusPublished - 2014

Bibliografisk information

Defence details

Date: 2014-09-19
Time: 13:15
Place: Getingevagen 60 Lund University, Kemicentrum, Hall B, Lund University, Lund

External reviewer(s)

Name: Nielsen, Jens Erik
Title: Dr
Affiliation: Senior Manager in Novozymes,Bagsvaerd Denmark

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The information about affiliations in this record was updated in December 2015.
The record was previously connected to the following departments: Theoretical Chemistry (S) (011001039)

Ämnesklassifikation (UKÄ)

  • Teoretisk kemi

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