Effects of Pressure and Temperature on the Atomic Fluctuations of Dihydrofolate Reductase from a Psychropiezophile and a Mesophile.

Qi Huang,Toshiko Ichiye,Russell Hemley,Jocelyn Rodgers

doi:10.3390/ijms20061452

Qi Huang, Toshiko Ichiye + Show 2 more

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https://doi.org/10.3390/ijms20061452

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Abstract

Determining the effects of extreme conditions on proteins from “extremophilic” and mesophilic microbes is important for understanding how life adapts to living at extremes as well as how extreme conditions can be used for sterilization and food preservation. 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 pressures and temperatures 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. However, the increase in fluctuations with pressure cannot be due to thermal energy, which remains constant, nor the compressive effects of pressure, but instead, the hydrogen bonds are also weakened. In addition, 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, which differ between the two.

Highlights

Determining the effects of temperature and pressure on proteins is important for understanding how extremophiles adapt to thrive under extreme conditions as well as how to kill pathogenic microbes using temperature or pressure (i.e., “pascalization” or high-pressure processing of foods)
quasiharmonic approximation for energy landscapes (QHAEL) analyses of the above mentioned molecular dynamics (MD) simulations of EcDHFR and MpDHFR [34] indicates that temperature widens the underlying local potential energy wells while pressure makes them steeper, which is consistent with the previous observation that the sub-nanosec timescale mean square fluctuations (MSF) decrease with pressure
The analysis showed that the underlying local potential energy wells of MpDHFR are softer than those of EcDHFR

Summary

Introduction

Determining the effects of temperature and pressure on proteins is important for understanding how extremophiles adapt to thrive under extreme conditions as well as how to kill pathogenic microbes using temperature (i.e., pasteurization of foods) or pressure (i.e., “pascalization” or high-pressure processing of foods). Our simulations of MpDHFR and EcDHFR bound to tetrahydrofolate (THF) at various combinations of temperatures (25 or 37 ◦C) and pressures (1 or 220 bar) indicate that MSF, on a timescale of ~10 ns, averaged over the heavy atoms of the protein, are potential markers for corresponding states behavior because they become similar at the PG and TG of the organism from which the DHFR was isolated [31].

Results

Conclusion