EXPLORING THE SPACE OF PROTEIN-FOLDING HAMILTONIANS - THE BALANCE OF FORCES IN A MINIMALIST BETA-BARREL MODEL

A rapid and effective method for obtaining thermodynamic quantities fo r Hamiltonians whose configurational space has not been examined throu gh a direct simulation has been developed. This approach extends the s cope of the weighted histogram analysis method and is applied to the e xploration of the balance of forces within the off-lattice Honeycutt-T hirumalai 46-mer beta-barrel model. Specificity is introduced into the long range hydrophobic interactions by scaling back the non-native at tractive component of the hydrophobic interactions through a scaling f actor lambda (0<lambda<1). Thermodynamic properties for incremental va lues of lambda are extrapolated from the sampling of the original (lam bda=l) Hamiltonian. The results were found to be in good agreement wit h the thermodynamic signatures obtained by direct simulations. Decreas ing the strength of the non-native attractive hydrophobic interactions leads to a more cooperative folding with the folding and collapse tem peratures nearly coinciding at lambda=0.0. The free energy surfaces we re also seen to become progressively smoother while retaining a pronou nced native well. Thus, this methodology may be used in the developmen t, refinement, and exploration of folding for off-lattice protein mode ls. (C) 1998 American Institute of Physics.