title: Mechanisms of Ligand-Protein Interaction in Sec-14-like Transporters Investigated by Computer Simulations.
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 α-tocopherol transfer protein (α-TTP). CRALBP is responsible for mobilisation and photo-protection of short-chain cis-retinoids in the dim-light visual cycle or rod photoreceptors. α-TTP is a key protein responsible for selection and retention of RRR-α-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.
authors.affiliation: Departement für Chemie und Biochemie Universität Bern Freiestrasse 3 CH-3012 Bern, Switzerland.
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Helbling
authors.affiliation: Departement für Chemie und Biochemie Universität Bern Freiestrasse 3 CH-3012 Bern, Switzerland.
authors.forename: Christos
authors.initials: C
authors.lastname: Lamprakis
authors.affiliation: Departement für Chemie und Biochemie Universität Bern Freiestrasse 3 CH-3012 Bern, Switzerland.
authors.forename: Walter
authors.initials: W
authors.lastname: Aeschimann
authors.affiliation: Departement für Chemie und Biochemie Universität Bern Freiestrasse 3 CH-3012 Bern, Switzerland.
authors.forename: Cristin S
authors.initials: CS
authors.lastname: Bolze
authors.affiliation: Departement für Chemie und Biochemie Universität Bern Freiestrasse 3 CH-3012 Bern, Switzerland. achim.stocker@dcb.unibe.ch.
authors.forename: Achim
authors.initials: A
authors.lastname: Stocker
authors.affiliation: 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.
authors.forename: Michele
authors.initials: M
authors.lastname: Cascella
mesh_terms: D000818:Animals; D001692:Biological Transport; D002352:Carrier Proteins / Q000494:pharmacology / Q000502:physiology*; D008024:Ligands; D011485:Protein Binding; D014815:Vitamins / Q000378:metabolism; D024502:alpha-Tocopherol
chemical_list: D002352:Carrier Proteins; D008024:Ligands; D014815:Vitamins; C017763:alpha-tocopherol transfer protein; D024502:alpha-Tocopherol