TY - JOUR
T1 - Hierarchy of folding and unfolding events of protein G, CI2, and ACBP from explicit-solvent simulations
AU - Camilloni, Carlo
AU - Broglia, Ricardo Americo
AU - Tiana, Guido
PY - 2011/1/28
Y1 - 2011/1/28
N2 - The study of the mechanism which is at the basis of the phenomenon of protein folding requires the knowledge of multiple folding trajectories under biological conditions. Using a biasing molecular-dynamics algorithm based on the physics of the ratchet-and-pawl system, we carry out all-atom, explicit solvent simulations of the sequence of folding events which proteins G, CI2, and ACBP undergo in evolving from the denatured to the folded state. Starting from highly disordered conformations, the algorithm allows the proteins to reach, at the price of a modest computational effort, nativelike conformations, within a root mean square deviation (RMSD) of approximately 1 . A scheme is developed to extract, from the myriad of events, information concerning the sequence of native contact formation and of their eventual correlation. Such an analysis indicates that all the studied proteins fold hierarchically, through pathways which, although not deterministic, are well-defined with respect to the order of contact formation. The algorithm also allows one to study unfolding, a process which looks, to a large extent, like the reverse of the major folding pathway. This is also true in situations in which many pathways contribute to the folding process, like in the case of protein G.
AB - The study of the mechanism which is at the basis of the phenomenon of protein folding requires the knowledge of multiple folding trajectories under biological conditions. Using a biasing molecular-dynamics algorithm based on the physics of the ratchet-and-pawl system, we carry out all-atom, explicit solvent simulations of the sequence of folding events which proteins G, CI2, and ACBP undergo in evolving from the denatured to the folded state. Starting from highly disordered conformations, the algorithm allows the proteins to reach, at the price of a modest computational effort, nativelike conformations, within a root mean square deviation (RMSD) of approximately 1 . A scheme is developed to extract, from the myriad of events, information concerning the sequence of native contact formation and of their eventual correlation. Such an analysis indicates that all the studied proteins fold hierarchically, through pathways which, although not deterministic, are well-defined with respect to the order of contact formation. The algorithm also allows one to study unfolding, a process which looks, to a large extent, like the reverse of the major folding pathway. This is also true in situations in which many pathways contribute to the folding process, like in the case of protein G.
U2 - 10.1063/1.3523345
DO - 10.1063/1.3523345
M3 - Journal article
C2 - 21280806
SN - 0021-9606
VL - 134
SP - 045105
JO - The Journal of Chemical Physics
JF - The Journal of Chemical Physics
IS - 4
ER -