Protein domain movements: detection of rigid domains and visualization of hinges in comparisons of atomic coordinates

Abstract

The activity of many proteins induces conformational transitions by hinge-bending, which involves the movement of relatively rigid parts of a protein about flexible joints. We present an algorithm to identify and visualize the movements of rigid domains about common hinges in proteins. In comparing two structures, the method partitions a protein into domains of preserved geometry. The domains are extracted by an adaptive selection procedure using least-squares fitting. The user can maintain the spatial connectivity of the domains and filter significant structural differences (domain movements) from noise in the compared sets of atomic coordinates. The algorithm subsequently characterizes the relative movements of the found domains by effective rotation axes (hinges). The method is applied to several known instances of domain movements in protein structures, namely, in lactoferrin, hexokinase, actin, the extracellular domains of human tissue factor, and the receptor of human growth factor. The results are visualized with the molecular graphics package VMD (Humphrey et al., J. Mol. Graphics 14(1):33-38, 1996). Applications of the algorithm to the analysis of conformational changes in proteins and to biomolecular docking are discussed.

Conformational flexibility of bacterial RNA polymerase

“…As described above, a large alteration of the Taq RNAP x-ray structure was required for an optimal fit to the E. coli cryo-EM structure. Partitioning of the structure into domains that move as rigid bodies was performed with the Hingefind algorithm (23). Using a maximum tolerance of 4 Å, the algorithm found six rigid domains that exhibited internal motions of 1.5 Å to 2.3 Å.…”

An Algorithmic Approach to the Identification of Rigid Domains in Proteins

“…In this paper, we propose a mathematical definition for the concept of rigid domain that has appeared in the literature [14,22,15,10,20] in mostly imprecise form. Using our definition, we present an efficient approximation algorithm for finding the rigid domains of a protein, given two conformations of the protein.…”

“…The identification of rigid domains is therefore useful in understanding the structure-function relationship of proteins. Many algorithms, including [14,22,15,10,20], have been developed to identify rigid domains.…”

“…These include the pioneering work by Gerstein et al [8], MolMovDB [7,14,5] by Gerstein et al, HingeFind [22] by Wrigger et al, DomainFinder [15,16] by Hinsen, DynDom [10,11,12,13] by Hayward et al,and [20] by Nichols et al Most of these papers consider more general problems than identifying rigid domains; for example, they including the one by Nichols et al More specifically, the descriptions of rigid domains in these papers include the following two characteristics: (1) the residues in a rigid domain move relatively rigidly; in other words, the residues in a domain move with similar rigid motions. (2) The distances of residues in a rigid domain are approximately conserved, i.e.…”

“…The identification of rigid domains is therefore useful in understanding the structure-function relationship of proteins. Many algorithms, including [14,22,15,10,20], have been developed to identify rigid domains.In this paper, we complement these works by proposing a mathematical definition of a rigid domain. We argue that our definition more accurately captures the intuitive notion of rigid domain in the previous work, than the quantitative definition of a rigid domain introduced by Nichols et al [20].…”