Dynamics of Lysozyme Structure Network: Probing the Process of Unfolding
Amit Ghosh 1, K. V. Brinda 2 and Saraswathi Vishveshwara 1*
1 Indian Institute of Science
2 Cornell University
* To whom correspondence should be addressed. E-mail: sv{at}mbu.iisc.ernet.in.
Submitted on October 23, 2006
Revised on November 20, 2006
Accepted on 12 December 2006
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Abstract |
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Recently we have shown that the three-dimensional structure of proteins can be investigated from the network perspective, where the amino acid residues are considered as the nodes in the network and the non-covalent interactions between them are considered for the edge-formation. In the present study, the dynamical behaviour of such networks has been examined by considering the example of T4-lysozyme. The equilibrium dynamics and the process of unfolding are followed by simulating the protein at 300K and at higher temperatures (400K, 500K) respectively. The snapshots of the protein structure from the simulations are represented as Protein Structure Networks (PSN) in which the strength of the non-covalent interactions is considered as an important criterion in the construction of edges. The profiles of the network parameters such as the degree distribution and the size of the largest cluster (giant component) have been examined as a function of interaction strength at different temperatures. Similar profiles are seen at all the temperatures. However, the critical strength of interaction (Icritical) and the size of the largest cluster at all interaction strengths have shifted to lower values at 500K. Further, folding/unfolding transition has been correlated with contacts evaluated at Icritical and with the composition of the top large clusters obtained at interaction strengths greater than Icritical. Finally, the results have been compared with experiments and predictions have been made about the residues, which are important for stability and folding. To summarize, the network analysis presented in this work has provided insights into the details of the changes occurring in the protein tertiary structure at the level of amino acid side-chain interactions, in both the equilibrium and the unfolding simulations. The method can also be employed as a valuable tool in the analysis of MD simulation data, since it captures the details at a global level, which may elude conventional pair-wise interaction analysis.
Key Words:
High temperature MD simulation, Largest cluster, Network analysis of protein structure, Protein structure network, Unfolding of Lysozyme, critical Interaction Strength
