Abstract:
Molecular Dynamics (MD) simulations are used to analyze the internal motions of proteins. In this thesis, the molecular dynamics trajectories of the apo form of dihydrofolate reductase (DHFR), and both apo and holo forms of triosephosphate isomerase (TIM) at three different temperatures, 200 K, 300 K and 400 K are examined. Analysis mainly consists of utilization of two methods: principal components analysis (PCA) to determine the collective protein fluctuations with high mean square fluctuations, and linear time series analysis to examine the collective vibrational motions in detail. Time series model parameters obtained for the free states of DHFR and TIM are similar, indicating the reliability of the analysis. It is found that at high temperatures collectivity reduces and global twisting motion seen in both proteins remarkably diminishes. At low temperatures, the important loop motions are reduced. Vibrational frequencies of the first 40 principal modes are extracted by time series analysis, and probability density functions of these frequencies are plotted to compare different MD runs. It is seen that simulations at higher temperatures have lower frequency distributions. Nevertheless, the difference between 300 K and 400 K is very small compared to the frequency shift from 200 K to 300 K. For its ligand bound form, TIM has higher frequencies than the free form at 200 K, as seen at 300 K in a previous study. However, ligand binding reduces the global twisting motion of the two monomers of TIM remarkably, which is opposite to what has been observed at 300 K. This shows that ligand binding may have different effects on the collective motions at different temperatures.
