RESUMO
Most of the current understanding of structure-property relations at the molecular and the supramolecular scales can be formulated in terms of the stability of and the interactions between a limited number of recurring structural motifs (e.g., H-bonds, coordination polyhedra, and protein secondary structure). Here we demonstrate an algorithm to automatically recognize such patterns, based on the identification of local maxima in the probability distributions observed in atomistic computer simulations, which is robust to the dimensionality and the sparsity of the reference atomistic data. We first discuss its main features, demonstrating some on artificial data sets, and then show how it can be applied to identify coordination environments in Lennard-Jones clusters and to recognize secondary-structure patterns in the simulation of an oligopeptide. To assess the applicability of this algorithm for motifs that involve several interdependent degrees of freedom, we also employ it to identify groups of conformers of the cluster and the polypeptide, considered in their entirety. The motifs identified by analyzing atomistic simulations can be used to interpret and rationalize the stability and behavior of the system at hand, and also as a tool to accelerate sampling, in association with biased molecular dynamics schemes.
RESUMO
Estimating the free energy of adsorption of materials-binding peptides is fundamental to quantify their interactions across bio/inorganic interfaces, but is difficult to achieve both experimentally and theoretically. We employ a combination of molecular dynamics (MD) simulations and dynamical force-spectroscopy experiments based on atomic force microscopy (AFM) to estimate the free energy of adsorption ΔGads of a (GCRL) tetrapeptide on amorphous SiO2 in pure water. The results of both equilibrium, advanced sampling MD and non-equilibrium, steered MD are compared with those of two different approaches used to extract ΔGads from the dependence of experimentally measured adhesion forces on the applied AFM loading rates. In order to obtain unambiguous peak forces and bond loading rates from steered MD trajectories, we have developed a novel numerical protocol based on a piecewise-harmonic fit of the adhesion work profile along each trajectory. The interpretation of the experiments has required a thorough quantitative characterization of the elastic properties of polyethylene glycol linker molecules used to tether (GCRL)15 polypeptides to AFM cantilevers, and of the polypeptide itself. All obtained ΔGads values fall within a relatively narrow window between -5 and -9 kcal mol(-1), but can be associated with large relative error bars of more than 50%. Among the different approaches compared, Replica Exchange with Solute Tempering simulations augmented with MetaDynamics (RESTMetaD) and fitting of dynamic force spectroscopy experiments with the model of Friddle and De Yoreo lead to the most reliable ΔGads estimates.
