Characterizing molecular flexibility by combining lRMSD measures.

The root mean square deviation (RMSD) and the least RMSD are two widely used similarity measures in structural bioinformatics. Yet, they stem from global comparisons, possibly obliterating locally conserved motifs. We correct these limitations with the so-called combined, which mixes independent RMSD measures, each computed with its own rigid motion. The combined RMSD is relevant in two main scenarios, namely to compare (quaternary) structures based on motifs defined from the sequence (domains, SSE), and to compare structures based on structural motifs yielded by local structural alignment methods. We illustrate the benefits of combined RMSD over the usual RMSD on three problems, namely (i) the assignment of quaternary structures for hemoglobin (scenario #1), (ii) the calculation of structural phylogenies (case study: class II fusion proteins; scenario #1), and (iii) the analysis of conformational changes based on combined RMSD of rigid structural motifs (case study: one class II fusion protein; scenario #2). Using these, we argue that the combined RMSD is a tool a choice to perform positive and negative discrimination of degree of freedom, with applications to the design of move sets and collective coordinates. Combined RMSD are available within the Structural Bioinformatics Library (https://sbl.inria.fr). This article is protected by copyright. All rights reserved.