Date Published: April 12, 2019
Publisher: Public Library of Science
Author(s): Yanzhen Hou, Jiaojiao Liu, Jianfeng He, Xubiao Peng, Antti J. Niemi, L. Michel Espinoza-Fonseca.
Protein dynamics is pivotal to biological processes. However, experiments are very demanding and difficult to perform, and all-atom molecular dynamics simulations can still not provide all the answers. This motivates us to analyze protein dynamics in terms of different reduced coordinate representations. We then need to resolve how to reconstruct the full all-atom dynamics from its coarse grained approximation. Accordingly we scrutinize all-atom molecular dynamics trajectories in terms of crystallographic Protein Data Bank (PDB) structures, and inquire to what extent is it possible to predict the dynamics of side chain Cβ atoms in terms of the static properties of backbone Cα and O atoms. Here we find that simulated Cβ dynamics at near physiological conditions can be reconstructed with very high precision, using the knowledge of the crystallographic backbone Cα and O positions. The precision we can reach with our PDB-based Statistical Method reconstruction exceeds that of popular all-atom reconstruction methods such as Remo and Pulchra, and is fully comparable with the precision of the highly elaborate Scwrl4 all-atom reconstruction method that we have enhanced with the knowledge of the backbone Cα and O atom positions. We then conclude that in a dynamical protein that moves around at physiological conditions, the relative positions of its Cβ atoms with respect to the backbone Cα and O atoms, deviate very little from their relative positions in static crystallographic PDB structures. This proposes that the dynamics of a biologically active protein could remain subject to very similar, stringent stereochemical constraints that dictate the structure of a folded crystallographic protein. Thus, our results provide a strong impetus to the development of coarse grained techniques that are based on reduced coordinate representations.
The Cα atoms are located at the branch points of a protein, they connect the backbone and the side chains. As a consequence their positions are subject to relatively tight stereochemical constraints. Indeed, in the case of static crystallographic proteins, the all-atom structure can be often determined with a good precision from the knowledge of the Cα positions [1–9]. This motivates the so-called Cα trace problem where the goal is to construct an accurate all-atom model of a crystallographic folded protein structure solely from the knowledge of the positions of its Cα atoms [10–15].
We report on results that we have obtained using our Statistical Method reconstruction algorithm, and the publicly available reconstruction algorithms Remo and Scwrl4. Since Scwrl4 requires that the peptide planes are known, we first construct the peptide planes using the Cα and O atom coordinates from the Anton simulation. We then estimate the positions of peptide plane C, N and H atoms using the ideal peptide plane structure shown in Fig 4. Accordingly we denote this enhanced variant ScwrIPP in the sequel. The present Statistical Method reconstruction algorithm will be denoted Stat in the sequel. Note that we do not use the full Anton peptide planes in ScwrIPP. This is so that the information content in ScwrIPP and Stat are comparable.
We have investigated dynamical proteins using results from all-atom molecular dynamics simulation, with Anton supercomputer. In particular, we have inspected the very long time period Anton simulation trajectories of villin and ww-domain. We have found that the Cβ positions along these trajectories can be accurately reconstructed, solely from the knowledge of the backbone Cα and O atom dynamics in combination with a statistical analysis of static crystallographic PDB structures.