Determining the effects of extreme conditions on proteins from “extremophilic” and mesophilic microbes is important for understanding how life adapts to living at extremes. Previous molecular dynamics simulations of dihydrofolate reductase (DHFR) from a psychropiezophile (cold- and pressure-loving), Moritella profunda (Mp), and a mesophile, Escherichia coli (Ec), at various combinations of growth pressure and temperature of the two organisms indicate that atomic fluctuations, which are important for enzyme function, increase with both temperature and pressure. Here, the factors that cause increases in atomic fluctuations in the simulations are examined. The fluctuations increase with temperature not only because of greater thermal energy and thermal expansion of the protein but also because hydrogen bonds between protein atoms are weakened. The increases in fluctuations with pressure, which cannot be due to thermal energy or the compressive effects of pressure, are correlated with the weakened hydrogen bonds. The results also suggest that temperature might affect external loops more strongly while pressure might affect motion between elements within the protein. In addition, the differences between MpDHFR and EcDFHR with respect to the change in loop subdomains are also examined here to study the adaptions of the proteins. Increased temperature causes larger increases in fluctuations of the loop regions of MpDHFR than EcDHFR, and increased pressure causes both increases and decreases in fluctuations of the loops. Analysis indicates that a flexible CD loop in MpDHFR is an adaptation for cold because it makes the adenosine binding subdomain more flexible. Analysis also indicates that the Thr113-Glu27 hydrogen bond in MpDHFR is an adaptation for high pressure because it provides flexibility within the loop subdomain compared to the very strong Thr113-Asp27 hydrogen bond in EcDHFR, and affects the correlation of the Met20 and GH loops.

Pressure and temperature effects in Escherichia coli and Moritella profunda dihydrofolate reductase

2019 Fall National Meeting

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