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Calculation of Apparent pKa Values of Saturated Fatty Acids with Different Lengths in DOPC Phospholipid Bilayers

Škulj, Sanja; Vazdar, Mario (2019) Calculation of Apparent pKa Values of Saturated Fatty Acids with Different Lengths in DOPC Phospholipid Bilayers. Physical Chemistry Chemical Physics, 21 (19). pp. 10052-10060. ISSN 1463-9076

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We performed all-atom molecular dynamics simulations and calculated free energy profiles and apparent pKa values for neutral and anionic forms of single myristic (C14:0), palmitic (C16:0) and stearic (C18:0) fatty acid embedded in the DOPC bilayer and explicit water solvent. We showed that neutral forms of fatty acids are stabilized inside the bilayer by hydrogen bonding of fatty acid carboxylic group with DOPC phosphate and carbonyl group. In contrast to the neutral form, anionic forms of fatty acids are shifted towards water-membrane interface and are instead stabilized by hydrogen bonding to interfacial water. By using umbrella sampling simulations, we calculated free energies of stabilization and revealed that free energy of stabilization inside the bilayer increases with the chain length for both neutral and deprotonated forms. On the other hand, free energies of flip-flop of both neutral and anionic forms are constant upon the prolongation of the fatty acid. Based on the free energy curves, we also calculated apparent fatty acid pKa, app values in the bilayer which are 7.0, 7.2 and 6.3 for myristic, palmitic and stearic acid and are increased by several pKa units compared to the corresponding pKa values in water. By further analysis of the calculated curves we found that spontaneous protonation of fatty acid anions takes place in the bilayer interior at ca. 1.4 nm from the bilayer center for all studied fatty acids.

Item Type: Article
Additional Information: This study was supported by Croatian Science Foundation, Project No. UIP-2014-09-6090. We thank the computer cluster Isabella based at SRCE - University of Zagreb, University Computing Centre for computational resources. We also thank Prof. Elena E. Pohl and Dr Zlatko Brkljac. a for useful comments and critical reading of the manuscript.
Uncontrolled Keywords: fatty acids ; lipid bilayer ; molecular dynamics ; pKa calculation
Subjects: NATURAL SCIENCES > Chemistry
Divisions: Division of Organic Chemistry and Biochemistry
Project titleProject leaderProject codeProject type
Molekularni aspekti oksidativnih procesa u stanicama-MolOxStressMario VazdarUIP-2014-09-6090HRZZ
Depositing User: Sanja Škulj
Date Deposited: 08 May 2020 06:54
DOI: 10.1039/C9CP01204D

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