Monte Carlo calculations of the free energy of binary sII hydrogen clathrate hydrates for identifying efficient promoter molecules.

The thermodynamics of binary sII hydrogen clathrates with secondary guest molecules is studied with Monte Carlo simulations. The small cages of the sII unit cell are occupied by one H(2) guest molecule. Different promoter molecules entrapped in the large cages are considered.

Reordering hydrogen bonds using hamiltonian replica exchange enhances sampling of conformational changes in biomolecular systems.

Hydrogen bonds play an important role in stabilizing (meta-)stable states in protein folding. Hence, they can potentially be used as a way to bias these states in molecular simulation methods. Previously, Wolf et al.

Modeling amyloid fibril formation: a free-energy approach.

Amyloid fibrils are structures consisting of many proteins with a well-defined conformation. The formation of these fibrils has been the subject of intense research, largely due to their connection to several diseases. We focus here on the computational studies and discuss these from a free-energy point of view.

Quantitative prediction of amyloid fibril growth of short peptides from simulations: calculating association constants to dissect side chain importance.

Quantitative prediction of the fibril growth properties of different peptides is conducted with a molecular dynamics approach. Association constants of small peptides used as a model for amyloid formation are calculated, and the results show very good agreement with experiments. Also the free-energy differences associated with two important interactions that characterize fibril growth, namely cross-beta-sheet and lateral interactions, are obtained.

Rapid free energy calculation of peptide self-assembly by REMD umbrella sampling.

We extend umbrella sampling with replica exchange steps to calculate free energies that are important in the self-assembly of peptides. This leads to a more than 10-fold speed up over conventional umbrella sampling, thereby providing a practical method to calculate these free-energy differences. This approach can also observe first-order phase transitions and pinpoint the location of the concomitant boundary.

Concentration dependence of alpha-synuclein fibril length assessed by quantitative atomic force microscopy and statistical-mechanical theory.

The initial concentration of monomeric amyloidogenic proteins is a crucial factor in the in vitro formation of amyloid fibrils. We use quantitative atomic force microscopy to study the effect of the initial concentration of human alpha-synuclein on the mean length of mature alpha-synuclein fibrils, which are associated with Parkinson's disease. We determine that the critical initial concentration, below which low-molecular-weight species dominate and above which fibrils are the dominant species, lies at approximately 15 muM, in good agreement with earlier measurements using biochemical methods.

The formation of fibrils by intertwining of filaments: model and application to amyloid Abeta protein.

We outline a model that describes the interaction of rods that form intertwined bundles. In this simple model, we compare the elastic energy penalty that arises due to the deformation of the rods to the gain in binding energy upon intertwining. We find that, for proper values of the bending Young's modulus and the binding energy, a helical pitch may be found for which the energy of intertwining is most favorable.

A statistical-mechanical theory of fibril formation in dilute protein solutions.

We outline a theoretical treatment that describes fibril formation in dilute protein solutions. For this, we combine a theory describing self-assembly and conformational transition with a description of the lateral association of linear chains. Our statistical-mechanical model is able to predict the mean degree of polymerization and the length of the fibrils and their precursors, as well as the weight fractions of the different aggregated species in solution.

Computational study of ground-state chiral induction in small peptides: comparison of the relative stability of selected amino acid dimers and oligomers in homochiral and heterochiral combinations.

The relative stabilities of homochiral and heterochiral forms of selected dipeptides, AA, AS, AC, AV, AF, AD, AK, tripeptides, AAA, AVA, and an acetylpentapeptide, AcGLSFA, have been calculated using thermodynamic integration protocols and the GROMOS 53A6 force field. Integration pathways have been designed that produce minimal disturbance to the system, including the use of soft atoms, low-energy intermediates, and chiral inversion of the smaller amino acid in the peptide. Comparison of the results obtained by thermodynamic integration between the diastereomeric forms (in explicit water, at 300 K) and from exhaustive global minimum-energy searches for the individual dipeptides (implicit water, epsilon = 78, 0 K) suggests that entropic contributions to the relative stability of the chiral forms are important.

Controlling the energy transfer in dipole chains.

Processing digital signals on the molecular scale is of great interest. In this paper, we discuss the control of pulselike energy propagation through one-dimensional arrays of dipoles. Three systems are explored.