Mixed Coarse-graining of Large Proteins Using Elastic Network Model

Download or read book Mixed Coarse-graining of Large Proteins Using Elastic Network Model written by Ayşe Özge Kürkçüoğlu and published by . This book was released on 2003 with total page 124 pages. Available in PDF, EPUB and Kindle. Book excerpt: Mixed coarse-graining approach to elastic network model of proteins has been introduced to enable the modeling of a protein's native conformation with regions of low and high resolution. This method is applied to two large proteins, Influenza virus hemagglutinin and b-galactocidase, with 1509 and 4044 residues, respectively. In the mixed-resolution model, each node of the elastic network represents the center of mass of a single residue (high-resolution) or a group of residues (low-resolution), and close-neighbouring nodes are connected by springs. As a result, the dynamics of the interesting parts within a large protein are analyzed at high resolution, while the rest of the structure is represented at lower resolution, thus keeping the total number of nodes in the system at a reasonable level for computational efficiency. Two parameters of the model, the cutoff radius and the force constant are calculated for hierarchical levels of uniform coarse-graining and further used in the mixed coarse-graining simulations. The calculated mean-square fluctuations are in good agreement with the fluctuations obtained from experimental temperature factors for the high resolution parts. The first mode shapes and modes of motion are obtained with high correlations for different levels of mixed coarse-grained proteins. It is also shown that similar frequency distributions are obtained at the lower end of the spectrum for different proteins and at different levels of coarse-graining. The results indicate that the vibrational dynamics of specific components in a large multi-subunit protein are described at best by retaining all the components in the structure at least at a lower resolution.