Sequence‐specific dynamic information in proteins

Abstract

We examine the local and global properties of the average B‐factor, 〈B〉, as a residue‐specific indicator of protein dynamic characteristics. It has been shown that values of 〈B〉 for the 20 amino acids differ in a statistically significant manner, and that, while strongly determined by the static physical properties of amino acids, they also encode averaged information about the influence of global fold on single‐residue dynamics. Therefore, complete sequences of amino acids also encode fold‐related global dynamic information, in addition to the local information that arises from static physical properties. We show that the relative magnitudes of these two contributions can be determined using Fourier methods, which represent the global properties of the sequences. It has also been shown that the behavior of Fourier components of 〈B〉 differs, with very high statistical significance, between structural groups, and that this information is not available from a comparable analysis of static amino acid properties.

The structure of protein dynamic space

“…Average B Factors. In this work, we use values of the residue-specific average B factor <B> which have been adjusted from our previous work (1), to account for the removal from our database of some defective sequences. The new values of <B(X)> are correlated with the previous values with R = 0.98, and all conclusions of our previous work remain.…”

Dynamic and conformational switching in proteins

“…That parameter must be based on actual dynamic data, must be residue-specific, and must distinguish between the 20 amino acids in a statistically significant manner. We have shown [10] that these requirements are satisfied by the amino-acid-specific average of the crystallographic B factor, which we denote (for amino acid X) by <B(X)>. The B factor gives a crystallographic estimate of the degree of motion of a specific atom, in this case, the alpha carbon of each amino acid.…”

“…They therefore contain more information about a specific amino acid than the per-residue mobility arising from simulation of any single protein. It was shown [10] that the distributions of B for the 20 amino acids, and the associated average values, which average over random differences between individual crystal structures, indeed differ from one another in a statistically significant manner.…”

“…[12][13][14][15][16] These methods are based on a signal processing approach, and were originally applied to analyses of the static physical properties of sequences. In recent work, [10,11] we studied the sequences of proteins written as strings of <B(X)> values. (We refer to these as dynamic sequences.)…”

“…Simulation methods, which are the current standard for the computational study of protein dynamics, are extremely processor-intensive, and it is generally possible, in the course of an investigation, to simulate only one protein, or a small set of proteins of interest. In recent work, [10,11] we have developed alternative, bioinformatic methods for the study of protein dynamics. These methods make it possible to study the dynamic characteristics of large datasets of proteins simultaneously, and to draw general conclusions based on those studies.…”