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Histone variants regulate replication, transcription, DNA damage repair, and chromosome segregation. Though widely accepted as a paradigm, it has not been rigorously demonstrated that histone variants encode unique mechanical properties. Here, we present a new theoretical approach called minimal cylinder analysis that uses strain fluctuations to determine the Young's modulus of nucleosomes from all-atom molecular dynamics simulations. Recently, we validated this computational tool against in vitro single-molecule nanoindentation of histon