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Previous studies have shown that most random amino acid substitutions destabilize protein folding (i.e. increase the folding free energy). No analogous studies have been carried out for protein-protein binding. Here we use a structure-based model of the major coat protein in a simple virus, bacteriophage φX174, to estimate the free energy of folding of a(More)
We extend replica-exchange simulation in two ways and apply our approaches to biomolecules. The first generalization permits exchange simulation between models of differing resolution--i.e., between detailed and coarse-grained models. Such "resolution exchange" can be applied to molecular systems or spin systems. The second extension is to "pseudoexchange"(More)
A promising method for calculating free energy differences DeltaF is to generate nonequilibrium data via "fast-growth" simulations or by experiments--and then use Jarzynski's equality. However, a difficulty with using Jarzynski's equality is that DeltaF estimates converge very slowly and unreliably due to the nonlinear nature of the calculation--thus(More)
We study the conformational equilibria of two peptides using a novel statistical mechanics approach designed for calculating free energy differences between highly dissimilar conformational states. Our results elucidate the contrasting roles of entropy in implicitly solvated leucine dipeptide and decaglycine. The method extends earlier work by Voter and(More)
The relationship between mutation, protein stability and protein function plays a central role in molecular evolution. Mutations tend to be destabilizing, including those that would confer novel functions such as host-switching or antibiotic resistance. Elevated temperature may play an important role in preadapting a protein for such novel functions by(More)
There is a great need for improved statistical sampling in a range of physical, chemical, and biological systems. Even simulations based on correct algorithms suffer from statistical error, which can be substantial or even dominant when slow processes are involved. Further, in key biomolecular applications, such as the determination of protein structures(More)
This report presents several approaches aimed at reducing the bias and uncertainty of the free energy difference estimates obtained using the thermodynamic integration simulation strategy. The central idea is to utilize interpolation schemes, rather than the often-used trapezoidal rule quadrature, to fit the thermodynamic integration data, and obtain a more(More)
The differential adhesion hypothesis of development states that patterning of organisms, organs and tissues is mediated in large part by expression of cell adhesion molecules. The cues provided by cell adhesion molecules are also hypothesized to facilitate specific connectivity within the nervous system. In this study we characterize a novel mouse mutation(More)
This report presents the application of polynomial regression for estimating free energy differences using thermodynamic integration data, i.e., slope of free energy with respect to the switching variable lambda. We employ linear regression to construct a polynomial that optimally fits the thermodynamic integration data, and thus reduces the bias and(More)
Molecular dynamics simulations were used to characterize the structure and dynamics for several peptides and the effect of conjugating them to a gold nanoparticle. Peptide structure and dynamics were compared for two cases: unbound peptides in water, and peptides bound to the gold nanoparticle surface in water. The results show that conjugating the peptides(More)