A Parallel Molecular Modeling Framework to Assess DNA Sequence Effects on Nucleosome Stability

Central to eukaryotic cellular support such as transcription regulation and chromatin structure are DNA interactions with the nucleosome histone core. The interactions of the histone core with DNA are currently understood partially at best, due in part to the wide range of DNA sequence effects involved in the formation of stable nucleosomes. This paper presents a high-performance computational modeling framework designed to enable greater understanding of DNA sequence effects on nucleosome stability through the automated generation of new DNA-histone configurations. The presented framework includes modules for the mutation of DNA sequences, use of those sequences in molecular simulation, and subsequent energy calculations. Parallel computing enables the configuration of a large number of nucleosome structures and modules are customizable for use in studies such as molecular dynamics. This paper discusses a prototype study using energy minimization to evaluate the high-throughput framework and address the computational feasibility and application to future studies of DNA sequence effects on nucleosome stability.