Analyzing Fluctuation Properties in Protein Elastic Networks with Sequence-Specific and Distance-Dependent Interactions

Abstract

Simple protein elastic networks which neglect amino-acid information often yield reasonable predictions of conformational dynamics and are broadly used. Recently, model variants which incorporate sequence-specific and distance-dependent interactions of residue pairs have been constructed and demonstrated to improve agreement with experimental data. We have applied the new variants in a systematic study of protein fluctuation properties and compared their predictions with those of conventional anisotropic network models. We find that the quality of predictions is frequently linked to poor estimations in highly flexible protein regions. An analysis of a large set of protein structures shows that fluctuations of very weakly connected network residues are intrinsically prone to be significantly overestimated by all models. This problem persists in the new models and is not resolved by taking into account sequence information. The effect becomes even enhanced in the model variant which takes into account very soft long-ranged residue interactions. Beyond these shortcomings, we find that model predictions are largely insensitive to the integration of chemical information, at least regarding the fluctuation properties of individual residues. One can furthermore conclude that the inherent drawbacks may present a serious hindrance when improvement of elastic network models are attempted.

Molecular dynamics analysis of biomolecular systems including nucleic acids

“…Various CG models for proteins and nucleic acids have been proposed; however, their accuracy and application are limited due to the simplified form, which forfeits microscopic details such as side-chain conformations and interactions [51]. Currently, applications of CG models are problem-dependent, and improvements in their use for proteins and nucleic acids have been in progress [52][53][54][55]. Furthermore, long fibers of DNA and chromatin have been modeled as polymer chains [56][57][58][59][60][61][62], and efficient simulation methods have been considered [63].…”

Molecular Dynamics Analysis of Biomolecular Systems Including Nucleic Acids

“…Of course, their accuracy and application are limited due to the simplified form; e.g., the conformation of the side-chain is lost in the amino-acid level coarse-graining, and hence microscopic details of interactions cannot be considered [58]. Currently, the best choice depends on the problem; while all-atom models are adopted for a wide variety of biomolecules, efforts to improve coarse-grained models of proteins and nucleic acids have been taken (including ours [59][60][61][62]).…”