Studyng the unfolding kinetics of proteins under pressure using long molecular dynamic simulation runs

CHARA OSVALDO; GRIGERA JOSÉ RAÚL; MCCARTHY ANDRÉS NORMAN

Journal of Biological Physics (J Biol Phys)

Springer

Lugar: Netherlands; Año: 2008 vol. 33 p. 515 - 522

0092-0606

The usefulness of computational methods such as molecular dynamics simulationhas been extensively established for studying systems in equilibrium. Nevertheless, itsapplication to complex non-equilibrium biological processes such as protein unfolding hasbeen generally regarded as producing results which cannot be interpreted straightforwardly.In the present study, we present results for the kinetics of unfolding of apomyoglobin,based on the analysis of long simulation runs of this protein in solution at 3 kbar (1 atm =1.01325, bar = 101 325 Pa). We hereby demonstrate that the analysis of the data collectedwithin a simulated time span of 0.18 μs suffices for producing results, which coincideremarkably with the available unfolding kinetics experimental data. This not only validatesmolecular dynamics simulation as a valuable alternative for studying non-equilibriumprocesses, but also enables a detailed analysis of the actual structural mechanism whichunderlies the unfolding process of proteins under elusive denaturing conditions such ashigh pressure.