The Root Mean Square Deviation of the simulated structures from the initial structural model showed the system stabilizes by ca 7 nsec. All the structures were analyzed with snapshots taken between 10 nsec�C20 nsec trajectory time. The Xmgrace software was used for numerical graphs and interpretation of data. Previously well studied closed and open forms of PTP1B were used for the MD simulations primarily as a control model to evaluate the success of the simulations . Cytoscape 2.3 was used to make the interaction map for the functionally important residues of the PTP domains . The conformational segments corresponding to the ten conserved PTP motifs were analysed for structural changes during MD simulations by measuring the root mean square fluctuations for each Ca atom as well as for each atom per residue over the MD simulation time . These fluctuations were also compared with those obtained for the PTP1B structures in the open and closed 129-56-6 conformations. Among the ten motifs, the fluctuations were maximal for motif 8 containing the WPD loop. As this loop must close upon substrate binding, the flexibility of this loop is essential for the phosphatase activity of the PTP domain. Overall, more fluctuations were observed for the D2 domains of both DLAR and PTP99A. The phosphotyrosine binding motif showed substantial fluctuations which were more pronounced for the D2 domains as opposed to the D1 domains of both DLAR and PTP99A. Overall, the motifs 2, 3, 4, 5, 6 and 7 showed less fluctuations when compared to other motifs for both domains of DLAR and PTP99A. Their lower kinetic fluctuations are perhaps expected, given that these motifs play a very important role in the folding and stability of the PTP domains . Spatially proximal residues were represented as N6N colour coded matrices . All the six PTP domains examined showed a similar matrix which could be interpreted as a signature of the PTP fold. This inter-atomic interaction map has a shape like a butterfly where the body and wing comprise of interactions concentrated around the motifs 2, 3, 4, 5, 6 and 7 which form the core of the PTP domain . The head of the butterfly pattern is made up of motif 1 whereas motifs 8, 9 and 10 form the tail. Interestingly, for all the six PTP domains analyzed, the body and the wings of the butterfly signature remain unperturbed.