On the relationship between the protein structure and protein dynamics

Abstract

Recently, we have developed a method (Shih et al., Proteins: Structure, Function, and Bioinformatics 2007;68: 34-38) to compute correlation of fluctuations of proteins. This method, referred to as the protein fixed-point (PFP) model, is based on the positional vectors of atoms issuing from the fixed point, which is the point of the least fluctuations in proteins. One corollary from this model is that atoms lying on the same shell centered at the fixed point will have the same thermal fluctuations. In practice, this model provides a convenient way to compute the average dynamical properties of proteins directly from the geometrical shapes of proteins without the need of any mechanical models, and hence no trajectory integration or sophisticated matrix operations are needed. As a result, it is more efficient than molecular dynamics simulation or normal mode analysis. Though in the previous study the PFP model has been successfully applied to a number of proteins of various folds, it is not clear to what extent this model will be applied. In this article, we have carried out the comprehensive analysis of the PFP model for a dataset comprising 972 high-resolution X-ray structures with pairwise sequence identity <or=25%. We found that in most cases the PFP model works well. However, in case of proteins comprising multiple domains, each domain should be treated separately as an independent dynamical module with its own fixed point; and in case of the protein complex comprising a number of subunits, if functioning as a biological unit, the whole complex should be considered as one single dynamical module with one fixed point. Under such considerations, the resultant correlation coefficient between the computed and the X-ray structural B-factors for the data set is 0.59 and 75% (727/972) of proteins with a correlation coefficient >or=0.5. Our result shows that the fixed-point model is indeed quite general and will be a useful tool for high throughput analysis of dynamical properties of proteins.

On the Relationship Between Residue Solvent Exposure and Thermal Fluctuations in Proteins

“…Here, we further compare RSA profiles with theoretical thermal fluctuations computed by two methods, the Protein-fixed-point (PFP) model (Shih et al, 2007;Lu et al, 2008) and Weighted-contact number (WCN) model . These two models are shown to be able to reproduce B-factor from protein structure.…”

“…The relationships between thermal fluctuation and some concepts related to ASA have been studied. B-factor has shown to correlate to local packing densities (Halle, 2002), atomic distance to protein center-of-mass (Shih et al, 2007;Lu et al, 2008) and residue depth (Zhang et al, 2009). Residue flexibility was known to be correlated to its ASA in single protein (Sheriff et al, 1985) or small dataset (Carugo & Argos, 1997).…”

On the Structural Characteristics of the Protein Active Sites and Their Relation to Thermal Fluctuations

“…Hwang and co-workers (Shih, Huang et al 2007;Lu, Huang et al 2008) showed that the correlation matrix C is well approximated by…”

“…ENM has recently become a popular tool to analyze protein dynamics (Zheng, Brooks et al 2007;Yang, Song et al 2009;Zheng & Thirumalai 2009). Recently, Hwang and co-workers (Shih, Huang et al 2007;Huang, Shih et al 2008;Lin, Huang et al 2008;Lu, Huang et al 2008) developed even simpler models to calculate the correlations between the atomic fluctuations in p r o t e i n s d i r e c t l y f r om their structures without using mechanical models, or performing energy minimization or matrix 56 diagonalization. They are the Protein Fixed-Point Model and the Weighted Contact Number Model, which will be discussed in the next sections.…”

“…The aim of this review is to show that this peculiar relationship between catalytic sites and the structure centroid or its network centrality can be accounted for by the dynamical properties of the catalytic residues, which are in general more rigid than other residues. In addition, we will discuss the recent studies (Halle 2002;Shih, Huang et al 2007;Huang, Shih et al 2008;Lin, Huang et al 2008;Lu, Huang et al 2008) on the surprisingly close link 54 between protein structure and its thermal fluctuations. These studies showed that the atomic thermal fluctuations and motional correlations can be extracted directly from protein structures without using any mechanical models.…”