Molecular dynamics simulation of protein folding by essential dynamics sampling: folding landscape of horse heart cytochrome c

FULL TEXT

I. Daidone, A. Amadei, D. Roccatano and A. Di Nola

A new method for simulating the folding process of a protein is reported. The method is based on the Essential Dynamics Sampling (EDS) technique. In EDS a usual molecular dynamics simulation is performed, but only those steps, not increasing the distance from a reference structure, are accepted. The distance is calculated in a configurational subspace defined by a set of generalized coordinates obtained by an essential dynamics analysis of an equilibrated trajectory. The method was applied to the folding process of horse heart cytochrome c, a protein with ~3000 degrees of freedom. Starting from structures, with a root mean square deviation of ~2 nm from the crystal structure, the correct folding was obtained, by utilizing "only" 106 generalized degrees of freedom, chosen among those accounting for the backbone carbon atoms motions, hence not containing any information on the side chains. The folding pathways found are in agreement with experimental data on the same molecule.

Addresses

Daidone, Di Nola: Univ Roma La Sapienza, Dept Chem, I-00185 Rome, Italy
Amadei: A, Univ Roma Tor Vergata, Dept Chem Sci & Technol, Via Ric Sci 1, I-00133 Rome, Italy
Roccatano:Univ Aquila, Dept Chem Chem Engn & Mat, I-67010 Coppito, Italy