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Volume 11
Journal of Proteomics & Bioinformatics
ISSN: 0974-276X
Structural Biology 2018
September 24-26, 2018
September 24-26, 2018 | Berlin, Germany
14
th
International Conference on
Structural Biology
Dynamically induced water transport through membrane co-transporters
Marko Sever
and
Franci Merzel
National Institute of Chemistry, Slovenia
Statement of the Problem:
In our work we focus on various systems of membrane co-transporters, which are similar in their
capacity to facilitate the movement of water across the cell membrane in addition to the transport of their native substrates.
Mainly we focus on the sodium glucose co-transporter 1 (hSGLT1) on which we plan to develop the methodologies that will be
transferred on other systems, probably LeuT homologues. Mechanism of water transport through membrane co-transporters
in not fully elucidated yet.
Methodology & Theoretical Orientation:
We utilized explicit molecular dynamics simulations of the studied biomolecular
systems. We calculated various time dependent parameters describing local structure of the water channel, including
thermodynamic, electrostatic and geometric aspects. The correlations between these parameters were determined, with the
final goal of better elucidating the mechanisms of water transport in these systems. The characteristic protein movements
present in the systems were identified with the use of normal mode analysis.
Results:
By using the method of normal mode analysis in conjunction with using a projection function, we found a significant
difference in the breathing character between the wild type SGLT1 and the dual mutant (F453C and Q457C) in the low
frequency region. The radial component of the breathing motion is more pronounced in the dual mutant relative to the wild
type which correlates with the higher water permeability found experimentally in case of dual mutant. This might indicate an
importance of concerted dynamical modes in the water transport in membrane proteins.
Conclusion & Significance:
The studied membrane co-transporter systems are promising targets or models for drug
development. Elucidating their conformational behavior in greater detail would have positive effect on drug development.
Marko Sever et al., J Proteomics Bioinform 2018, Volume 11
DOI: 10.4172/0974-276X-C2-116
Figure 1:
Breathing character of vibrational modes.
Figure 2:
Representation of the protein hSGLT1with its substrates.