Book of Abstracts: Albany 2007
June 19-23 2007
Dynamics of Lysozyme Structure Network: Probing the Process of Unfolding
Understanding the process of protein folding continues to be challenging task in computational biology. Currently, the protein folding process is often monitored by calculating various reaction coordinates, such as the fraction of native contacts, the radius of gyration, the root mean square deviation, number of hydrogen bonds, etc. In the present study, we have explicitly considered the side-chain interactions by using the concept of protein structure networks and the unfolding process has been examined by tracking down the changes in the network properties. The dynamical behavior of such networks has been examined by considering the example of Bacteriophage T4-lysozyme. The equilibrium properties of the protein structure network are derived from the 300K simulation. The process of unfolding at high temperatures (400K and 500K) has been investigated by comparing the changes in the network properties with respect to the 300K simulation.
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. We observe a critical strength of interaction (Icritical) at which there is a transition in the size of the largest cluster. Although the transition profiles at all temperatures show behavior similar to those found in the crystal structures, the 500K simulations show that the non-native structures have lower Icritical values. Based on the interactions evaluated at Icritical value, the folding/unfolding transition region has been identified from the 500K simulation trajectories. Furthermore, the residues in the largest cluster obtained at interaction strength higher than Icritical have been identified to be important for folding. Thus, the compositions of the top largest clusters in the 500K simulations have been monitored to understand the dynamical processes such as folding/unfolding and domain formation/disruption. The results correlate well with experimental findings. In addition, the highly connected residues in the network have been identified from the 300K and 400K simulations and have been correlated with the protein stability as determined from mutation experiments. Based on these analyses, certain residues, on which experimental data is not available, have been predicted to be important for the folding and the stability of the protein.
References and Footnotes
Molecular Biophysics Unit