Bioinformatics BI_W0009

Title : STRUCTURAL BIOINFORMATICS AND MODELLING OF MEMBRANE PROTEINS.
Author : Gregorio Fernández Ballester
Year : 2008
Place of publish : Soria, Spain
Abstract :

 The determination of structures and dynamics events of membrane proteins is important for the
understanding of their function. The difficulties to obtain high resolution structures of integral
membrane proteins have boosted the development of computational approaches to tackle the
prediction of structure-function relationships. Among others, sequence alignment, motif
prediction, transmembrane segment identification, protein topology predictions and homology
modelling are the most widely used. Molecular modelling is a powerful tool for the prediction
of homologue sequences provided that 3D structure of a family member is known. This is the
case for some bacterial and eukaryotic channels that have been used as starting points for
detailed simulation studies of human channels that enhance our understanding on the ion
permeation and selectivity mechanisms. The 3D models are very useful in interpreting and
rationalising experimental data and to propose hypothesis that can be tested in the bench. In
addition, modelling of protein-ligand or protein-protein complexes can be used to explore and
exploit the pharmacology of the human channels through the study of compounds that interact
with receptors. These studies can lead to the discovery of novel therapeutics, or understand the
assembly of multicomponent protein complexes within the cell.
The limits of this technique rely on the quality of the models produced since this is biased
towards the template used, and exposed loops are extremely difficult to model, thus providing
uncertainty. These limitations, together with the scare amount of high resolution experimental
information available, may hamper accurate and reliable predictions. Although much remains
to be done, the computational approaches have much to contribute to our understanding of
structural biology.
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