Proteins with the ability to specifically bind strontium would potentially be of great use in the field of nuclear waste management. Unfortunately, no such peptides or proteins are known ? indeed, it is uncertain whether they exist under natural conditions due to low environmental concentrations of strontium. To investigate the possibility of devising such molecules, one of us (CV), in a previous experimental study [J. Biol. Inorg. Chem. 8, 334-40 (2003)], proposed starting from an EF-hand motif of the protein calmodulin and mutating some residues to change the motif?s specificity for calcium into one for strontium. In this paper, which represents a theoretical complement to the experimental work, we analyzed small-molecule crystallographic structures and performed quantum chemical calculations to identify possible mutations. We then constructed seven mutant sequences of the EF-hand motif and analyzed their dynamical and binding behaviors using molecular dynamics simulations and free-energy calculations (using the MM/PBSA method). As a result of these analyzes we were able to isolate some characteristics that could lead to mutant peptides with enhanced strontium affinity.

Key words: Calmodulin EF-hand motif, MM/PBSA free energy calculations, Molecular dynamics simulations, Mutated peptides, Strontium-binding peptides.