Allostery is a universal phenomenon that couples the information induced by a 
local perturbation (effector) in a protein to spatially distant regulated sites. 
Such an event can be described in terms of a large scale transmission of 
information (communication) through a dynamic coupling between structurally 
rigid (minimally frustrated) and plastic (locally frustrated) clusters of 
residues. To elaborate a rational description of allosteric coupling, we propose 
an original approach - MOdular NETwork Analysis (MONETA) - based on the analysis 
of inter-residue dynamical correlations to localize the propagation of both 
structural and dynamical effects of a perturbation throughout a protein 
structure. MONETA uses inter-residue cross-correlations and commute times 
computed from molecular dynamics simulations and a topological description of a 
protein to build a modular network representation composed of clusters of 
residues (dynamic segments) linked together by chains of residues (communication 
pathways). MONETA provides a brand new direct and simple visualization of 
protein allosteric communication. A GEPHI module implemented in the MONETA 
package allows the generation of 2D graphs of the communication network. An 
interactive PyMOL plugin permits drawing of the communication pathways between 
chosen protein fragments or residues on a 3D representation. MONETA is a 
powerful tool for on-the-fly display of communication networks in proteins. We 
applied MONETA for the analysis of communication pathways (i) between the main 
regulatory fragments of receptors tyrosine kinases (RTKs), KIT and CSF-1R, in 
the native and mutated states and (ii) in proteins STAT5 (STAT5a and STAT5b) in 
the phosphorylated and the unphosphorylated forms. The description of the 
physical support for allosteric coupling by MONETA allowed a comparison of the 
mechanisms of (a) constitutive activation induced by equivalent mutations in two 
RTKs and (b) allosteric regulation in the activated and non-activated STAT5 
proteins. Our theoretical prediction based on results obtained with MONETA was 
validated for KIT by in vitro experiments. MONETA is a versatile analytical and 
visualization tool entirely devoted to the understanding of the 
functioning/malfunctioning of allosteric regulation in proteins - a crucial 
basis to guide the discovery of next-generation allosteric drugs.