Abstract
We investigate the relationship between the motions of the same peptide loop segment incorporated within a protein structure and motions of free or end-constrained peptides. As a reference point we also compare against alanine chains having the same length as the loop. Both the analysis of atomic molecular dynamics trajectories and structure-based elastic network models, reveal no general dependence on loop length or on the number of solvent exposed residues. Rather, the whole structure affects the motions in complex ways that depend strongly and specifically on the tertiary structure of the whole protein. Both the Elastic Network Models and Molecular Dynamics confirm the differences in loop dynamics between the free and structured contexts; there is strong agreement between the behaviors observed from molecular dynamics and the elastic network models. There is no apparent simple relationship between loop mobility and its size, exposure, or position within a loop. Free peptides do not behave the same as the loops in the proteins. Surface loops do not behave as if they were random coils, and the tertiary structure has a critical influence upon the apparent motions. This strongly implies that entropy evaluation of protein loops requires knowledge of the motions of the entire protein structure.
Highlights
A longstanding point of view has been that the dynamics of protein loops might be modeled as if they were polymers capable of randomly sampling their various degrees of freedom
We present a detailed analysis of the dynamic trajectories based on atomic Molecular Dynamics and show that these motions closely resemble those computed with ElasticNetwork Models (ENMs), the Anisotropic Network Models (ANM) [12]
In this work we investigate the relationships between loop motions and the motions of protein structures
Summary
A longstanding point of view has been that the dynamics of protein loops might be modeled as if they were polymers capable of randomly sampling their various degrees of freedom. Network Models (ENMs) where the loops are observed to move in strong correlation with the large domains of the structures From these we have even suggested that the functional loops move with the slow domain motions, and not with any significant independence. Flory [2] gave an explanation for the formation of the small rings or coils based on various statistical parameters In this present work, we aim to see whether this random point of view has any validity for protein loops when tested against atomic Molecular Dynamics (MD), and we compare the MD dynamical freedom, representing the entropies of the loops, to see which extreme viewpoint is more likely, either the random viewpoint or the controlled behavior from the elastic models. In the present study we consider a small set of diverse protein structures, to investigate the behavior of their protein loops, and show that their motional behaviours are far from random, show a high level of complexity and a strong dependence upon the tertiary structure
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