Weighted ensemble simulations of biomolecules: Applications to peptides and proteins*

Weighted ensemble (WE) method is an efficient way to numerically sample rare event trajectories generated by random dynamical systems, first introduced by Huber and Kim [1] and further extended by Zuckerman and coworkers [2].
We apply this method to a small peptide called chignolin, which only has 10 amino acids but is known to have at least two stable states, a folded and misfolded states. The main focus is to study the transitions between these two states of chignolin, and to extract the kinetic properties of chignolin at high temperature [3]. While applying the WE method, we use the diffusion map (a manifold learning technique) coordinates as order parameters and compare the result with those using more chemically intuitive coordinates (hydrogen bond distances). Furthermore, we also apply the WE method to proline isomerization of PIN1 enzyme and the global conformational change of adenylate kinase.

[1] G.A. Huber and S. Kim, Biophys. J. 70 (1996) 97-110.
[2] D.M. Zuckerman and L.T. Chong, Annu. Rev. Biophys. 46 (2017) 43-57.
[3] H. Fujisaki, K. Moritsugu, A. Mitsutake, and H. Suetani, J. Chem. Phys. 149 (2018) 134112.