Open AccessMechanisms of Ligand–Protein Interaction in Sec-14-like Transporters Investigated by Computer Simulations
Author(s) -
Rachel E. Helbling,
Christos Lamprakis,
Walter Aeschimann,
Cristin S. Bolze,
Achim Stocker,
M. Cascella
Publication year - 2014
Publication title -
chimia
Language(s) - English
Resource type - Journals
eISSN - 2673-2424
pISSN - 0009-4293
DOI - 10.2533/chimia.2014.615
Subject(s) - ligand (biochemistry) , chemistry , biophysics , transport protein , transporter , microbiology and biotechnology , computational biology , biology , biochemistry , receptor , gene
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.