Publication

Role of charge and hydrophobicity in liprotide formation: A molecular dynamics study with experimental constraints

Nedergaard Pedersen, J., Wilhelmus Johannes Maria Frederix, P., Skov Pedersen, J., Marrink, S. J. & Otzen, D., 2018, In : ChemBioChem. 19, p. 263–271 9 p.

Research output: Contribution to journalArticleAcademicpeer-review

Copy link to clipboard

Documents

  • Role of Charge and Hydrophobicity in Liprotide Formation

    Final publisher's version, 1.13 MB, PDF document

    Request copy

DOI

  • Jannik Nedergaard Pedersen
  • Pim Wilhelmus Johannes Maria Frederix
  • Jan Skov Pedersen
  • Siewert Jan Marrink
  • Daniel Otzen

Bovine α-lactalbumin (aLA) and oleate (OA) form a complex that has been intensively studied for its tumoricidal activity. Small-angle X-ray scattering (SAXS) has revealed a lipid core surrounded by partially unfolded protein. We call this type of complex a liprotide. Little is known of the molecular interactions between OA and aLA and no technique has so far provided any high resolution structure of liprotides. Here, we used coarse grained (CG) molecular dynamics (MD) simulations, Isothermal titration calorimetry (ITC) and SAXS to investigate the interactions between aLA and OA during the process of liprotide formation. By using ITC we found that the strongest enthalpic interactions occurred at a molar ratio of 12.0 ± 1.4 OA/aLA. Liprotides formed between OA and aLA at several OA/aLA ratios in silico were stable in both CG and all-atom simulations. We have calculated SAXS spectra from the simulated structures which show good agreement with experimentally measured patterns of matching liprotides. The simulations showed that aLA assumes a molten globular (MG) state, exposing several hydrophobic patches involved in interactions with OA. Initial binding of aLA to OA occurs in an area of aLA where a high amount of positive charge is located and only later hydrophobic interactions become important. Our findings suggest a general mechanism for liprotide formation and may explain the ability of a large number of proteins to form liprotides with OA.

Original languageEnglish
Pages (from-to)263–271
Number of pages9
JournalChemBioChem
Volume19
Early online date20-Nov-2017
Publication statusPublished - 2018

    Keywords

  • COMPLEXES, HAMLET, HUMAN ALPHA-LACTALBUMIN, X-RAY-SCATTERING, OLEIC-ACID, TUMOR-CELLS, FORCE-FIELD, FATTY-ACID, PROTEIN INTERACTIONS, MOLTEN GLOBULE

ID: 50363932