This Article Full Text Full Text (PDF) Supplemental All Versions of this Article: biophysj.105.074997v1 90/8/2706    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Sacquin-Mora, S. Articles by Lavery, R. Search for Related Content PubMed PubMed Citation Articles by Sacquin-Mora, S. Articles by Lavery, R.

Investigating the Local Flexibility of Functional Residues in Hemoproteins

Laboratoire de Biochimie Théorique, UMR 9080 CNRS, Institut de Biologie Physico-Chimique, Paris, France

Correspondence: Address reprint requests to Richard Lavery, Laboratoire de Biochimie Théorique, UMR 9080 CNRS, Institut de Biologie Physico-Chimique, 13 rue Pierre et Marie Curie, 75005 Paris, France. E-mail: rlavery{at}ibpc.fr.

It is now widely accepted that protein function depends not only on structure, but also on flexibility. However, the way mechanical properties contribute to catalytic mechanisms remains unclear. Here, we propose a method for investigating local flexibility within protein structures that combines a reduced protein representation with Brownian dynamics simulations. An analysis of residue fluctuations during the dynamics simulation yields a rigidity profile for the protein made up of force constants describing the ease of displacing each residue with respect to the rest of the structure. This approach has been applied to the analysis of a set of hemoproteins, one of the functionally most diverse protein families. Six proteins containing one or two heme groups have been studied, paying particular attention to the mechanical properties of the active-site residues. The calculated rigidity profiles show that active site residues are generally associated with high force constants and thus rigidly held in place. This observation also holds for diheme proteins if their mechanical properties are analyzed domain by domain. We note, however, that residues other than those in the active site can also have high force constants, as in the case of residues belonging to the folding nucleus of c-type hemoproteins.