Comparison of sequence-based and structure-based energy functions for the reversible folding of a peptide

¹ University of Zurich
² University of Cambridge

^* To whom correspondence should be addressed. E-mail: paci{at}bioc.unizh.ch.

Submitted on October 29, 2004
Revised on December 13, 2004
Accepted on 8 February 2005

	Abstract

We used computer simulations to compare the reversible folding of a 20-residue peptide, as described by sequence-based and structure-based energy functions. Sequence-based energy functions are transferable and can be used to describe the behaviour of different proteins, since interactions are defined between atomic species. Structure-based energy functions instead are not transferable, as the interactions are defined relative to the native conformation, which is assumed to correspond to the global minimum of the energy. Our results indicate that the sequence-based and the structure-based descriptions are in qualitative agreement in characterising the two-state behaviour of the peptide that we studied. We also found, however, that several equilibrium properties, including the free energy landscape, can be significantly different in the various models. These results suggest that the fact that a model reproduces correctly the native state of a polypeptide chain does not imply that the thermodynamic and kinetic properties will also be described correctly.

Key Words: CHARMM, Go models, force fields, free energy surfaces, protein folding

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