F. Marty Ytreberg

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We introduce a straightforward, single-ensemble, path sampling approach to calculate free energy differences based on Jarzynski's relation. For a two-dimensional "toy" test system, the new (minimally optimized) method performs roughly one hundred times faster than either optimized "traditional" Jarzynski calculations or conventional thermodynamic(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 level of the p53 transcription factor is negatively regulated by the E3 ubiquitin ligase murine double-minute clone 2 (MDM2). The interaction between p53 and MDM2 is essential for the maintenance of genomic integrity for most eukaryotes. Previous structural studies revealed that MDM2 binds to p53 transactivation domain (p53TAD) from residues 17 to 29.(More)
We present a detailed comparison of computational efficiency and precision for several free energy difference (DeltaF) methods. The analysis includes both equilibrium and nonequilibrium approaches, and distinguishes between unidirectional and bidirectional methodologies. We are primarily interested in comparing two recently proposed approaches, adaptive(More)
One reason that free energy difference calculations are notoriously difficult in molecular systems is due to insufficient conformational overlap, or similarity, between the two states or systems of interest. The degree of overlap is irrelevant, however, if the absolute free energy of each state can be computed. We present a method for calculating the(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)
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)
We compute the absolute binding affinities for two ligands bound to the FKBP protein using nonequilibrium unbinding simulations. The methodology is straightforward requiring little or no modification to many modern molecular simulation packages. The approach makes use of a physical pathway, eliminating the need for complicated alchemical decoupling schemes.(More)
Developing a comprehensive description of the equilibrium structural ensembles for intrinsically disordered proteins (IDPs) is essential to understanding their function. The p53 transactivation domain (p53TAD) is an IDP that interacts with multiple protein partners and contains numerous phosphorylation sites. Multiple techniques were used to investigate the(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)