Simulated Annealing with Tsallis Weights - A Numerical Comparison

We discuss the use of Tsallis generalized mechanics in simulated annealing algorithms. For a small peptide it is shown that older implementations are not more effective than regular simulated annealing in finding ground state configurations. We propose a new implementation which leads to an improvement over regular simulated annealing.Comment: Late

Stochastic dynamics simulations in a new generalized ensemble

We develop a formulation for molecular dynamics, Langevin, and hybrid Monte Carlo algorithms in the recently proposed generalized ensemble that is based on a physically motivated realisation of Tsallis weights. The effectiveness of the methods are tested with an energy function for a protein system. Simulations in this generalized ensemble by the three methods are performed for a penta peptide, Met-enkephalin. For each algorithm, it is shown that from only one simulation run one can not only find the global-minimum-energy conformation but also obtain probability distributions in canonical ensemble at any temperature, which allows the calculation of any thermodynamic quantity as a function of temperature.Comment: to appear in Chem. Phy. Let

Solvation model dependency of helix-coil transition in polyalanine

Helix-coil transitions in poly-alanine molecules of length 10 are studied by multicanonical Monte Carlo simulations. The solvation effects are included by either a distance-dependent dielectric permittivity or by a term that is proportional to the solvent-accessible surface area of the peptide. We found a strong dependence of the characteristics of the helix-coil transition from the details of the solvation model.Comment: to appear in Biophysical Journa

Large Fatty Acid-Derived Aβ42 Oligomers Form Ring-Like Assemblies

As the primary toxic species in the etiology of Alzheimer disease (AD) are low molecular weight oligomers of Aβ, it is crucial to understand the structure of Aβ oligomers for gaining molecular insights into AD pathology. We have earlier demonstrated that in the presence of fatty acids, Aβ42 peptides assemble as 12-24mer oligomers. These Large Fatty Acid-derived Oligomers (LFAOs) exist predominantly as 12mers at low and as 24mers at high concentrations. The 12mers are more neurotoxic than the 24mers and undergo self-replication, while the latter propagate to morphologically distinct fibrils with succinct pathological consequences. In order to glean into their functional differences and similarities, we have determined their structures in greater detail by combining molecular dynamic simulations with biophysical measurements. We conjecture that the LFAO are made of Aβ units in an S-shaped conformation, with the 12mers forming a double-layered hexamer ring (6 × 2) while the structure of 24mers is a double-layered dodecamer ring (12 × 2). A closer inspection of the (6 × 2) and (12 × 2) structures reveals a concentration and pH dependent molecular reorganization in the assembly of 12 to 24mers, which seems to be the underlying mechanism for the observed biophysical and cellular properties of LFAOs

Comparative Study of Multicanonical and Simulated Annealing Algorithms in the Protein Folding Problem

We compare a few variants of the recently proposed multicanonical method with the well known simulated annealing for the effectiveness in search of the energy global minimum of a biomolecular system. For this we study in detail Met-enkephalin, one of the simplest peptides. We show that the new method not only outperforms simulated annealing in the search of the energy groundstate but also provides more statistical-mechanical information about the system.Comment: to be published in Physica A, LATEX 32 pages, figures available on reques

Recent results from generalized-ensemble protein-folding simulations

With the development of generalized-ensemble techniques, an efficient sampling of low-energy configurations and calculation of accurate low-temperature thermodynamic quantities became feasible for proteins and peptides. The generalized-ensemble technique utilized is related to Tsallis generalized mechanics formalism. It is used to examine the picture for the folding kinetics as proposed from the simulations of minimal models. For this purpose, the characteristic temperatures of folding for the pentapeptide Metenkephalin were investigated

Generalized ensembles: A new way of simulating proteins

I review the generalized ensemble approach for simulation of peptides and proteins. These molecules are frustrated systems with a complicated energy landscape. The resulting slowing down in numerical simulations is alleviated by our ansatz. © 1998 Elsevier Science B.V. All rights reserved

Computer simulation of biological macromolecules in generalized ensembles

For many years the emphasis in protein-folding simulations has been laid as to how to predict the three-dimensional structure of proteins. Only recently has there be a shift in interest towards the thermodynamics of folding. We show that generalized-ensemble techniques are well suited to study both questions for realistic protein models

Sampling protein energy landscapes - The quest for efficient algorithms

© Springer Science+Business Media, LLC 2011. All rights reserved. Computer simulations aim to become virtual microscopes that can probe the working of cells on a molecular level. One of the remaining obstacles is still poor sampling. This chapter reviews strategies for faster sampling and discusses their limitations. Recent applications to protein folding document the utility of the described techniques