Understanding the relation between protein flexibility, stability and function remains one of the most challenging, open questions in biophysical chemistry. For example, proteins need to be flexible to facilitate substrate binding but locally rigid to sustain substrate specificity. Enzymes from microorganisms that thrive at elevated temperatures, also referred to as thermophiles, are a natural study-case to dig into the issue. These proteins are stable and functional at a high temperature regime but generally lack activity at ambient conditions. Therefore, their thermal stability has been correlated to enhanced mechanical rigidity through the so-called corresponding states paradigm introduced years ago by Somero. The generality of this view, however, has been questioned by a number of experimental and computational studies. Computer simulations based on the molecular dynamics technique offer a unique opportunity to explore the correlation among mechanical rigidity and thermophilicity. In our recently published article in PLoS One we consider the specific case of two tetrameric orthologous malate dehydrogenase proteins from two bacteria that grow optimally at different temperatures. For these orthologues, as for other oligomeric proteins, the role of interfacial interactions becomes critical, adding up to the other cohesive forces acting on monomeric proteins. How the protein rigidity/flexibility patterns influence the stability and function of the two molecules is discussed in detail in the paper.
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| Dehydrogenases are proteins that require a cofactor in order to catalyze a reaction. The picture above depicts one monomer of a lactate dehydrogenase in a cofactor-bound (holoprotein) and a cofactor-unbound (apoprotein) form. |
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