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Amino-acid solvation structure in transmembrane helices from molecular dynamics simulations
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
2006 (English)In: Biophysical Journal, ISSN 0006-3495, Vol. 91, no 12, 4450-4463 p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
2006. Vol. 91, no 12, 4450-4463 p.
Keyword [en]
Amino Acids/*chemistry, Cell Membrane, Computer Simulation, Hydrogen Bonding, Membrane Proteins/*chemistry, Models; Molecular, Protein Folding, Protein Structure; Secondary, Water/chemistry
URN: urn:nbn:se:su:diva-11255DOI: 10.1529/biophysj.106.092767PubMedID: 17012325OAI: diva2:177774
Available from: 2008-01-10 Created: 2008-01-10 Last updated: 2010-01-14Bibliographically approved
In thesis
1. Solvation properties of proteins in membranes
Open this publication in new window or tab >>Solvation properties of proteins in membranes
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Knowledge about the insertion and stabilization of membrane proteins is a key step towards understanding their function and enabling membrane protein design. Transmembrane helices are normally quite hydrophobic to insert efficiently, but there are many exceptions with unfavorable polar or titratable residues. Since evolutionary conserved these amino acids are likely of paramount functional importance, e.g. the four arginines in the S4 voltage sensor helix of voltage-gated ion channels. This has lead to vivid discussion about their conformation, protonation state and cost of insertion. To address such questions, the main focus of this thesis has been membrane protein solvation in lipid bilayers, evaluated using molecular dynamics simulations methods.

A main result is that polar and charged amino acids tend to deform the bilayer by pulling water/head-groups into the hydrophobic core to keep their hydrogen bonds paired, thus demonstrating the adaptiveness of the membrane to allow specific and quite complex solvation. In addition, this retained hydration suggests that the solvation cost is mainly due to entropy, not enthalpy loss. To further quantify solvation properties, free energy profiles were calculated for all amino acids in pure bilayers, with shapes correlating well with experimental in vivo values but with higher magnitudes. Additional profiles were calculated for different protonation states of the titratable amino acids, varying lipid composition and with transmembrane helices present in the bilayer. While the two first both influence solvation properties, the latter seems to be a critical aspect. When the protein fraction in the models resemble biological membranes, the solvation cost drops significantly - even to values compatible with experiment.

In conclusion, by using simulation based methods I have been able to provide atomic scale explanations to experimental results, and in particular present a hypothesis for how the solvation of charged groups occurs.

Place, publisher, year, edition, pages
Stockholm: Department of Biochemistry and Biophysics, Stockholm University, 2009. 62 p.
membrane protein, lipid bilayer, free energy, solvation, insertion, molecular dynamics simulations, protein mass fraction
National Category
Theoretical Chemistry
Research subject
urn:nbn:se:su:diva-27437 (URN)978-91-7155-856-5 (ISBN)
Public defence
2009-06-12, Magnelisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 12, Stockholm, 13:00 (English)
Available from: 2009-05-22 Created: 2009-05-04 Last updated: 2013-07-09Bibliographically approved

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