Specific Non-Local Interactions Are Not Necessary for Recovering Native Protein Dynamics

Abstract

The elastic network model (ENM) is a widely used method to study native protein dynamics by normal mode analysis (NMA). In ENM we need information about all pairwise distances, and the distance between contacting atoms is restrained to the native value. Therefore ENM requires O(N2) information to realize its dynamics for a protein consisting of N amino acid residues. To see if (or to what extent) such a large amount of specific structural information is required to realize native protein dynamics, here we introduce a novel model based on only O(N) restraints. This model, named the ‘contact number diffusion’ model (CND), includes specific distance restraints for only local (along the amino acid sequence) atom pairs, and semi-specific non-local restraints imposed on each atom, rather than atom pairs. The semi-specific non-local restraints are defined in terms of the non-local contact numbers of atoms. The CND model exhibits the dynamic characteristics comparable to ENM and more correlated with the explicit-solvent molecular dynamics simulation than ENM. Moreover, unrealistic surface fluctuations often observed in ENM were suppressed in CND. On the other hand, in some ligand-bound structures CND showed larger fluctuations of buried protein atoms interacting with the ligand compared to ENM. In addition, fluctuations from CND and ENM show comparable correlations with the experimental B-factor. Although there are some indications of the importance of some specific non-local interactions, the semi-specific non-local interactions are mostly sufficient for reproducing the native protein dynamics.

Explicit versus implicit consideration of binding partners in protein–protein complex to elucidate intrinsic dynamics

“…Following various established formalisms (Wilson et al 1955;Field 2007;Fuglebakk et al 2013;Dasgupta et al 2014a), we describe how NMA is performed using ENMs as a general method in this section. NMA captures vibrational signature of a given protein structure, assuming the harmonic approximation.…”

“…Liang and Dill 2001). An additional application of the ENM-based method was previously outlined by Dasgupta et al(Dasgupta et al 2014a) where a protein molecule is treated with more liquid-like properties and the effect of solvation was treated implicitly. The potential for implicitly treating non-protein partner molecules, such as water, to the intrinsic dynamics of proteins increases the potential for deeper insight into the mechanical in uence of solvent on proteins.…”