Biology Reference
In-Depth Information
receptor (
Floquet et al., 2010
), and an analysis of rhodopsin dimerization (
Niv &
Filizola, 2008
), which is shortly reviewed in the succeeding text.
To help understand the effect of oligomerization on the dynamics of GPCRs, Niv
and Filizola (
Niv & Filizola, 2008
) compared the motion of monomeric, dimeric, and
tetrameric arrangements of the prototypic GPCR rhodopsin. They used approximate,
however powerful, NMA technique, that is, elastic network model (ENM), to differ-
entiate between putative dynamic mechanisms, which may be responsible for the re-
cently reported conformational rearrangement of the TM4,5-TM4,5 dimerization
interface of GPCRs, which takes place during the process of receptor activation.
They also found the considerable perturbation of the normal modes of the rhodopsin
monomer during oligomerization, which was visible at the studied interface. Further-
more, they noticed increased positive correlation among the transmembrane domains
and between the extracellular loop and transmembrane regions of the rhodopsin pro-
tomer and highest interresidue positive correlation at the interfaces between proto-
mers (
Niv & Filizola, 2008
).
5.3.2
Software
NMA can be performed with MD software such as GROMACS (
Hess, Kutzner, van
der Spoel, & Lindahl, 2008
). Also, there are web-based tools available that may be
used by nonexperts. These include ElN´mo server (
Suhre & Sanejouand, 2004
) and
NOMAD-Ref server (
Lindahl, Azuara, Koehl, & Delarue, 2006
).
ElN´mo server is a web interface to the ENM that is designed as a fast and simple
tool to compute, visualize, and analyze low-frequency normal modes of large mac-
romolecules (
Suhre & Sanejouand, 2004
). Furthermore, there is no upper limit to the
size of the proteins that can be calculated. ElN´mo server may be used for compu-
tation of 100 lowest-frequency modes for a protein and results in descriptive param-
eters and visualizations, including degree of collectivity of movement, residue mean
square displacements, distance fluctuation maps, and the correlation between ob-
served and normal mode-derived atomic displacement parameters (
b
-factors)
(
Suhre & Sanejouand, 2004
).
NOMAD-Ref server enables online calculation of the normal modes of large mol-
ecules (up to 100,000 atoms), enabling a full all-atom representation of their structures,
parallel with an access to several programs that utilize these collective motions for de-
formation and refinement of biomolecular structures (
Lindahl et al., 2006
).
5.4
ELECTROSTATICS STUDIES
5.4.1
Background and examples of application
Electrostatic forces are one of the main determinants of molecular interactions. They
help guiding the folding of proteins, increase the binding of one protein to another,
and facilitate protein-DNA and protein-ligand binding (
Callenberg et al., 2010
). It
has been also shown that electrostatics influences various aspects of nearly all
