Free University Of Berlin Fb-Chemie, Takustrasse 6, Berlin, D-14195, GERMANY
A new Monte Carlo (MC) method is presented, which allows to simulate the folding process of small model peptides in a realistic manner. Key point of the method is the use of an all atom, off-lattice protein model with rigid bond lengths, bond angles and amide planes. Hence, the only degrees of freedom of the polypeptide backbone are the (phi,psi)-torsion angles. An elementary MC move is performed by co-operative rotations in a small window of consecutive amide planes, leaving the polypeptide conformation outside of the window invariant. These window MC moves generate local conformational changes only. Thus, large conformational changes of a polypeptide evolve gradually in time, if these MC moves are applied randomly many times.
To account for the lack of flexibility in the employed protein model a potential of mean force is used for the (phi,psi)-torsion angles. It is derived from molecular dynamics (MD) simulations of a flexible dipeptide using a conventional MD energy function. To avoid exaggeration of hydrogen bonding strengths for rigid polypeptide models, the electrostatic interactions involving hydrogen atoms are scaled down at short distances by 15% as compared to MD energy functions. With these adjustments of the energy function the rigid polypeptide model exhibits the same equilibrium distributions as does a fully flexible model with MD simulation.
The MC method is applied to a model peptide of 26 residues which represent the central part of the helix-turn-helix motive of ROP (Hoffmann & Knapp, 1996). Starting from a stretched beta-strand conformation pieces of alpha-helical structure form quickly. It follows a hydrophobic collapse in a compact conformation where the turn appears but is displaced. Then in a slow process of self-reptation the turn moves to its native-like position. The final conformation of the model polypeptide agrees with the ROP structure within the uncertainties of the energy function used.
References:
Protein Dynamics with Off-Lattice Monte Carlo Moves, Hoffman, D., Knapp,
E.W., Phys. Rev. E53 (1996) 4221-4224.