Selective Excitation of Native Fluctuations during Thermal Unfolding Simulations: Horse Heart Cytochrome c as a Case Study
Danilo Roccatano*,
Isabella Daidone1, Marc-Antoine Ceruso2,
Cecilia Bossa1 and Alfredo Di Nola1
Biophysical Journal 84:1876-1883 (2003)
*Dipartimento di Chimica,
Ingegneria Chimica e Materiali Universita' degli studi, 67010
L'Aquila, Italy;
1Department of Chemistry, University
of Rome, 00185 Rome, Italy; and
2Department of
Physiology and Biophysics, Mount Sinai School of Medicine, New York,
New York USA
Correspondence: Address reprint requests to Alfredo
Di Nola, E-mail: dinola@degas.chem.uniroma1.it.
The effect of temperature on the activation of native fluctuation motions during molecular dynamics unfolding simulations of horse heart cytochrome c has been studied. Essential dynamics analysis has been used to analyze the preferred directions of motion along the unfolding trajectories obtained by high temperature simulations. The results of this study have evidenced a clear correlation between the directions of the deformation motions that occur in the first stage of the unfolding process and few specific essential motions characterizing the 300 K dynamics of the protein. In particular, one of those collective motions, involved in the fluctuation of a loop region, is specifically excited in the thermal denaturation process, becoming progressively dominant during the first 500 ps of the unfolding simulations. As further evidence, the essential dynamics sampling performed along this collective motion has shown a tendency of the protein to promptly unfold. According to these results, the mechanism of thermal induced denaturation process involves the selective excitation of one or few specific equilibrium collective motions.