Conformational Behavior of Genetically-Engineered Dodecapeptides as a Determinant of Binding Affinity for Gold

Genetically engineered solid binding peptides, because of their unique affinity and specificity for solid materials, represent a promising molecular toolbox for nanoscience and nanotechnology. Despite their potential, the physicochemical determinants of their high affinity for surfaces remain, in most cases, poorly understood. Here we present experimental data and classical atomistic molecular dynamics simulations for two gold binding dodecapeptides (AuBP1 and AuBP2, Hnilova, M. et al. Langmuir 2008, 24, 12440) and a control peptide that does not bind to gold, to unravel the key microscopic differences among them. In particular, by means of extensive sampling via replica exchange simulations, we show here that the conformational ensemble of the three peptides in solution and on the gold surface can be examined, and that the role played by their different conformational flexibility can be analyzed. We found, specifically, that AuBP1 and AuBP2 are much more flexible than the control peptide, which allows all the potential Au-binding amino acids present in these AuBPs to concurrently bind to the gold surface. On the contrary, the potential Au-binding amino acids in the rigid control peptide cannot contact the surface all at the same time, hampering the overall binding. The role of conformational flexibility has been also analyzed in terms of the configurational entropy of the free and adsorbed peptides. Such analysis suggests a possible route to improve upon current flexible gold binding peptides.