Evaluating a coarse-grained IDP-model for structure and dynamics

Abstract: In this study a coarse-grained model of intrinsically disordered proteins (IDPs) is evaluated to determine whether the model is suitable to use for analyzing the structure and dynamics of IDPs. IDPs are proteins that lack a stable tertiary structure which gives them a flexible structure. The aim with this study is to find a model that is appropriate to use for analyzing dynamics events of IDPs. To evaluate if the model is appropriate to use, the structural characteristics of the protein are examined to verify that the generated results are consistent with previous studies. With a good model it will be possible to achieve a deeper understanding about these proteins, which is of considerable importance since IDPs are involved in several vital biological processes in eukaryotes. In this study, a specific model, primarily described by Das et al [1], is evaluated whether it can be used as a suitable model. To evaluate the model, the results from different simulations, with the IDP Histatin 5 [2] used as the model protein, will be compared and analyzed. Running several simulations with different set-ups of parameters from the original model will give a deeper understanding of how these parameters affect the conformation and flexibility of the IDP, and thus give the ability to improve the model. The simulations were performed by using the molecular dynamics package GROMACS [3]. To evaluate if the model is appropriate to use for analyzing the structure and dynamics of IDPs, the results from the different simulations are compared with protein contact maps and experimental data from small angle X-ray scattering. The results from a reference simulation, a simulation where there were as few changes as possible from the original model, indicates that the simulated Histatin 5 resembles a globular protein rather than an IDP that would have been the desired result. The conclusion can be drawn that the original model is not suitable to use for examining dynamic events of IDPs, but additional simulations have to be performed since some deviations made from the original model could have affected the results and thus the conclusion. Four simulations with different set-ups of the parameters from the original model are performed in this study. The results from these simulations indicate that there are clear differences in the behavior of the simulated proteins compared to the protein simulated in the reference simulation. Most of the parameter changes made in this study gave a satisfactory result, where the properties of the simulated protein are more similar to an IDP than to a globular protein. This study is only a first step in the process of finding a suitable model to be able to examine both the structure and the dynamics of IDPs. The work has to be continued in order to find an appropriate model for this purpose and there are several simulations that could be performed to continue this study.