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Thermal unfolding of alpha-lactalbumin at acidic pH: Insights from molecular dynamics simulations
Elena Ermakova1, Rauf Kurbanov1, Igor Sedov2
1Kazan Institute of Biochemistry and Biophysics, FRC Kazan Scientific Center of RAS, 2/31 Lobachevsky Str., 420111, Kazan, Russia.
Abstract:
The transformation of globular proteins into fibrils passes through several stages, including the formation of partially expanded conformational states different from the native or fully unfolded forms. Here we used molecular dynamics simulations to characterize the thermal unfolding of alpha-lactalbumin on the microsecond timescale in the range of temperatures of 300-440 K. Comparative analysis of structural changes, mobility of different parts of protein, and pathways through the free energy landscape during the unfolding of alpha-lactalbumin at different temperatures reveals the existence of several intermediate states separated by small energy barriers. The lifetime of these intermediates depends on temperature and varies from nanoseconds to microseconds.
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