%0 Journal Article
%A Zhang, Liqun
%A Centa, Thomas
%A Buck, Matthias
%D 2015
%T Structure
and Dynamics Analysis on Plexin-B1 Rho GTPase
Binding Domain as a Monomer and Dimer
%U https://acs.figshare.com/articles/journal_contribution/Structure_and_Dynamics_Analysis_on_Plexin_B1_Rho_GTPase_Binding_Domain_as_a_Monomer_and_Dimer/2035749
%R 10.1021/jp503668k.s001
%2 https://acs.figshare.com/ndownloader/files/3607062
%K signal pathways
%K Different analysis methods
%K L 1 loop
%K signal pathway 2
%K L 4 loop
%K F 90
%K NH
%K L 2 loop
%K RBD monomer
%K L 4 loop functions
%K CH
%K RMSF results show
%K NAMD
%K Rho GTPase binding domain
%K CO
%K network analysis method
%K Transfer entropy calculations
%K residues Q 25
%X Plexin-B1 is a single-pass transmembrane
receptor. Its Rho GTPase
binding domain (RBD) can associate with small Rho GTPases and can
also self-bind to form a dimer. In total, more than 400 ns of NAMD
molecular dynamics simulations were performed on RBD monomer and dimer.
Different analysis methods, such as root mean squared fluctuation
(RMSF), order parameters (S2), dihedral
angle correlation, transfer entropy, principal component analysis,
and dynamical network analysis, were carried out to characterize the
motions seen in the trajectories. RMSF results show that after binding,
the L4 loop becomes more rigid, but the L2 loop and a number of residues
in other regions become slightly more flexible. Calculating order
parameters (S2) for CH, NH, and CO bonds
on both backbone and side chain shows that the L4 loop becomes essentially
rigid after binding, but part of the L1 loop becomes slightly more
flexible. Backbone dihedral angle cross-correlation results show that
loop regions such as the L1 loop including residues Q25 and G26, the
L2 loop including residue R61, and the L4 loop including residues
L89–R91, are highly correlated compared to other regions in
the monomer form. Analysis of the correlated motions at these residues,
such as Q25 and R61, indicate two signal pathways. Transfer entropy
calculations on the RBD monomer and dimer forms suggest that the binding
process should be driven by the L4 loop and C-terminal. However, after
binding, the L4 loop functions as the motion responder. The signal
pathways in RBD were predicted based on a dynamical network analysis
method using the pathways predicted from the dihedral angle cross-correlation
calculations as input. It is found that the shortest pathways predicted
from both inputs can overlap, but signal pathway 2 (from F90 to R61)
is more dominant and overlaps all of the routes of pathway 1 (from
F90 to P111). This project confirms the allosteric mechanism in signal
transmission inside the RBD network, which was in part proposed in
the previous experimental study.
%I ACS Publications