<h3>Title</h3>
<p><span style="color: #0000ff;">Tracking Protein Dynamics in Atomistic MD simulations</span></p>
<p><strong><span style="text-decoration: underline;">Abstract</span> :</strong></p>
<p>Proteins undergo thermally driven dynamical motions on their potential energy surface (PES) which are crucial for biological function, like DNA replication, catalysis and cell signalling. Molecular dynamics (MD) simulations present a powerful tool to computationally sample the PES of a protein and visualize protein dynamics. However, despite the development of techniques to obtain dynamical information from MD trajectories such as principal component analysis (PCA),<sup>[1]</sup> time-structured independent component analysis (TICA),<sup>[2]</sup> and autoencoders,<sup>[3]</sup> the following questions still remain unaddressed: (1) How deterministic/stochastic is protein dynamics? (2) which set of motions are involved during non-equilibrium transitions between different PES minima, and (3) how does protein dynamics evolve with time as a protein samples the PES? In this work, we developed a PCA based metric to study the time-evolution of protein dynamics in MD trajectories. The new metric when applied together with a previously developed energylandscape sensitive measure,<sup>[4]</sup> provides us with unprecedented insights on changes in protein dynamics as it samples the PES. We demonstrate attractive features of the metric on model PES sampled using Monte Carlo (MC) simulations, and on MD trajectories of ubiquitin,<sup>[4]</sup> Aβ42 and HIV protease.<sup> [5]</sup> We foresee the metrics to be useful to study functional aspects of proteins such as enzyme catalysis and allostery. Our metrics can also be potentially used to accelerate MD simulations.</p>
<p>References:</p>
<p>1. David, C. C. &amp; Jacobs, D. J. Methods Mol. Biol. 1084, 193–226 (2014).</p>
<p>2. Naritomi, Y. &amp; Fuchigami, S. J. Chem. Phys. 134, 065101 (2011).</p>
<p>3. Wehmeyer, C. &amp; Noé, F. J. Chem. Phys. 148, 241703 (2018).</p>
<p>4. Paul, S., Ainavarapu, S. R. K. &amp; Venkatramani, R. J. Phys. Chem. B 124, 4247–4262 (2020).</p>
<p>5. Badaya, A. &amp; Sasidhar, Y. U. Sci. Rep. 10, 1–15 (2020).</p>