BIOPHYSICAL THEORY AND MODELING |
Investigating the local flexibility of functional residues in hemoproteins
Sophie Sacquin-Mora 1 and Richard Lavery 1*
1 Institut de Biologie Physico-Chimique
* To whom correspondence should be addressed. E-mail: rlavery{at}ibpc.fr.
Submitted on September 23, 2005
Revised on October 28, 2005
Accepted on 29 December 2005
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Abstract |
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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 (BD) simulations. An analysis of residue fluctuations during the BD 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 di-heme 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.
Key Words:
Active site residues, Brownian dynamics, Flexibility, Protein domains, Protein mechanics
