Mechanisms of Ligand–Protein Interaction in Sec-14-like Transporters Investigated by Computer Simulations

Authors

  • Rachel E. Helbling Departement für Chemie und Biochemie Universität Bern Freiestrasse 3 CH-3012 Bern, Switzerland
  • Christos Lamprakis Departement für Chemie und Biochemie Universität Bern Freiestrasse 3 CH-3012 Bern, Switzerland
  • Walter Aeschimann Departement für Chemie und Biochemie Universität Bern Freiestrasse 3 CH-3012 Bern, Switzerland
  • Cristin S. Bolze Departement für Chemie und Biochemie Universität Bern Freiestrasse 3 CH-3012 Bern, Switzerland
  • Achim Stocker Departement für Chemie und Biochemie Universität Bern Freiestrasse 3 CH-3012 Bern, Switzerland. achim.stocker@dcb.unibe.ch
  • Michele Cascella Department of Chemistry and Centre for Theoretical and Computational Chemistry (CTCC) University of Oslo PO BOX 1033 Blindern 0315 Oslo, Norway. michele.cascella@kjemi.uio.no

DOI:

https://doi.org/10.2533/chimia.2014.615

Keywords:

Molecular dynamics, Qm/mm, Metadynamics, Retinal, Tocopherol

Abstract

We review our recent work on protein–ligand interactions in vitamin transporters of the Sec-14-like protein. Our studies focused on the cellular-retinaldehyde binding protein (CRALBP) and the ?-tocopherol transfer protein (?-TTP). CRALBP is responsible for mobilisation and photo-protection of short-chain cis-retinoids in the dim-light visual cycle or rod photoreceptors. ?-TTP is a key protein responsible for selection and retention of RRR-?-tocopherol, the most active isoform of vitamin E in superior animals. Our simulation studies evidence how subtle chemical variations in the substrate can lead to significant distortion in the structure of the complex, and how these changes can either lead to new protein function, or be used to model engineered protein variants with tailored properties. Finally, we show how integration of computational and experimental results can contribute in synergy to the understanding of fundamental processes at the biomolecular scale.

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Published

2014-09-24

How to Cite

[1]
R. E. Helbling, C. Lamprakis, W. Aeschimann, C. S. Bolze, A. Stocker, M. Cascella, Chimia 2014, 68, 615, DOI: 10.2533/chimia.2014.615.