Although it is well known that both stability and flexibility are necessary for enzymes to function, general quantitative measures of flexibility have yet to emerge, which makes design of functional enzymes difficult. For flexibility, collective motions are important, but are the atomic fluctuations that give rise to collective motions more fundamentally important? Examining enzymes from “extremophilic” organisms that live under extreme conditions is a powerful method to explore this question. Extremophiles must maintain enzyme activity under extreme conditions to grow, and often the adaptations necessary for stability and flexibility conflict. While enzymes from extremophiles who live under extremes of temperature have been well-studied, enzymes from piezophiles who live at high pressure have not been, in part because high pressure is a difficult variable in the field and in the laboratory. However, experimental evidence is that pressure affects proteins differently than temperature, and new collection methods and high-pressure instrumentation makes experimental studies of high pressure effects on piezophile enzymes possible. Our molecular dynamics simulations of homologous enzymes from mesophiles and piezophiles under different conditions indicate that adaptation may appear even in nanosecond timescale atomic fluctuations. In addition, our new quasi-harmonic analysis method, which explores the energy landscape, have identified differences between enzymes from a piezophile and a mesophile in the underlying local motions as well as the collective motions. These differences are quantitated in terms of glass transition temperatures and intrinsic compressibilities and thermal expansivities.

Exploring the flexibility of extremophile enzymes by molecular dynamics simulations

255th National Meeting (2018)

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