Computational methods comprise a valuable tool to close the sequence –
structure gap, especially for membrane proteins. At this stage secondary
structure prediction programs are available to identify putative stretches of
helical transmembrane domains (TMDs) while a few programs are developed to
predict a beta sheet fold as the membrane spanning motif. With the knowledge
about the putative TMDs, here adopting a helical motif, at hand these TMDs can
be assembled into a tertiary structure, and finally into putative quaternary
structures using docking approaches
As a test case, viral channel forming proteins (VCPs), sometimes also
called viroporins, are used to develop strategies to generate plausible
structures [1]. VCPs are about five time smaller than human ion channels and
therefore used as a miniaturized system to investigate how ion channels are
formed. Using E5 protein of human papilloma virus type 16 (HPV-16) the assembly
of a poytopic membrane protein with three TMDs is presented in its hexameric
form [2]. Using a docking approach, the monomeric form is generated first
before assembling into the hexamer. The quality of the model is assessed using
potential of mean force calculations (PMF) identifying weak ion selectivity.
Principle component analysis (PCA) of the data from a classical molecular
dynamics simulations reveal asymmetric dynamics of the monomers. These dynamics
are compared with those derived for other VCPs such as polytopic p7 of
hepatitis C virus (HCV) with two TMDs [3] and bitopic M2 of influenza A [4].
Finally, coarse grained simulations are applied to probe the formation of the
quaternary structure of e.g. Vpu of HIV-1 [5].
Submitted by,
Dr.Wolfgang B. Fischer,
Institute of Biophotonics,
School of Biomedical Science and Engineering,
National Yang-Ming University,
Taipei, Taiwan
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