Computational Drug Discovery and Design

limitations linked with the identification of specific key residues

for protein function. For example, SPM can only identify resi-

dues which affect the global motion of proteins, while SCA is

not suitable for highly conserved residues. Therefore, instead

of searching for some other methods to predict hot spot resi-

dues with a different approach than previous in silico methods,

we assume that network analysis of the 3D structures is quite

suitable for the identification of allosteric hot spots in the target

proteins.

6. With the reliable format of representing network (nodes and
   their connectivity), the centrality values can also be calculated
   using Gephi [50], an open source software for exploring and
   manipulating networks. The residue interaction graph in 2D
   can be visualized with Force Atlas layout implemented in
   Gephi.

6 5 4

4

4

3

3

3

3

2

1

1

0.11

0.32

0.19

0.38

0.0

0.0

0.0

0.0

0.01 0.29

0.03

1

0.17

0.62

(A)

(B)

x y

x y

Fig. 2An exemplary graph showing the importance of betweenness centrality.

(a) Degree centrality and (b) betweeness centrality values calculated for each

node are shown

Molecular Dynamics Approach for Investigation of GPCR Allostery 469