An Algorithmic Approach to the Identification of Rigid Domains in Proteins

Abstract

Many proteins undergo conformational changes to perform their functions. A simple mechanism of conformational change in proteins is a rigid domain motion, in which two parts of a structure move rigidly with respect to each other. 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]. Furthermore, our definition admits a practical approximation algorithm. We can prove theoretical guarantee on the quality of the output of our algorithm. We implement a randomized version of our algorithm, and demonstrate its effectiveness on several known protein complexes.

Using least median of squares for structural superposition of flexible proteins

“…The Lesk's sieve-fit procedure [ 19 ] is unsuitable for superposition between two conformations with multiple rigid domains. HingeFind, presented by Wriggers et al [ 20 , 38 ], modified the sieve-fit routine so that the new atoms that are within tolerance distance are included in addition to the elimination of far apart atoms. Gerstein et al [ 18 ] proposed the fit-all algorithm to classify the mechanism of domain rotation as hinge-like or shear-like.…”