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The eukaryotic genome is packaged into a nucleus in the form of chromatin. The fundamental structural unit of chromatin is a protein-DNA complex, the nucleosome, where 146 or 147 base pairs of DNA wrap 1.75 times around a histone core. To function in cellular processes, however, nucleosomal DNA must be unwrapped. Although this unwrapping has been experimentally investigated, details of the process at an atomic level are not yet well understood. Here, we used molecular dynamics simulation with an enhanced sampling method to calculate the free energy profiles for unwrapping the outer superhelical turn of nucleosomal DNA. A free energy change of about 11.5 kcal/mol for the unwrapping agrees well with values obtained in single molecule experiments. This simulation revealed a variety of conformational states, indicating there are many potential paths to outer superhelicdal turn unwrapping, but the dominant path is likely asymmetric. At one end of the DNA, the first five bps unwrap, after which a second five bps unwrap at the same end with no increase in free energy. The unwrapping then starts at the other end of the DNA, where 10 bps are unwrapped. During further unwrapping of 15 bps, the unwrapping advances at one of the ends, after which the other end of the DNA unwraps to complete the unwrapping of the outer superhelical turn. These results provide insight into the construction, disruption, and repositioning of nucleosomes, which are continuously ongoing during cellular processes. [ABSTRACT FROM AUTHOR]

ERmod is a software package to efficiently and approximately compute the solvation free energy using the method of energy representation. Molecular simulation is to be conducted at two condensed-phase systems of the solution of interest and the reference solvent with test-particle insertion of the solute. The subprogram ermod in ERmod then provides a set of energy distribution functions from the simulation trajectories, and another subprogram slvfe determines the solvation free energy from the distribution functions through an approximate functional. This article describes the design and implementation of ERmod, and illustrates its performance in solvent water for two organic solutes and two protein solutes. Actually, the free-energy computation with ERmod is not restricted to the solvation in homogeneous medium such as fluid and polymer and can treat the binding into weakly ordered system with nano-inhomogeneity such as micelle and lipid membrane. ERmod is available on web at . © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

A novel, efficient sampling method for biomolecules is proposed. The partial multicanonical molecular dynamics (McMD) was recently developed as a method that improved generalized ensemble (GE) methods to focus sampling only on a part of a system (GEPS); however, it was not tested well. We found that partial McMD did not work well for polylysine decapeptide and gave significantly worse sampling efficiency than a conventional GE. Herein, we elucidate the fundamental reason for this and propose a novel GEPS, adaptive lambda square dynamics (ALSD), which can resolve the problem faced when using partial McMD. We demonstrate that ALSD greatly increases the sampling efficiency over a conventional GE. We believe that ALSD is an effective method and is applicable to the conformational sampling of larger and more complicated biomolecule systems. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]