MONTE-CARLO SIMULATIONS OF PROTEIN-FOLDING USING INEXACT POTENTIALS -HOW ACCURATE MUST PARAMETERS BE IN ORDER TO PRESERVE THE ESSENTIAL FEATURES OF THE ENERGY LANDSCAPE

Background: Monte Carlo simulations of the cubic lattice protein model with engineered sequences were performed in order to address the issu e of potential accuracy required for folding. The potential used for s equence selection played the role of the 'real' potential and differen t levels of inaccuracy were introduced by addition of noise. Results: The dependence of successful folding probability on potential noise wa s found to be sigmoidal and sequence-specific and can be described by an expression analytically derived from a simple theoretical model in which the density of states of the system contains a continuous region approximated by a Gaussian distribution separated from the unique nat ive conformation by a large energy gap. Conclusions: The decrease in f olding probability with potential inaccuracy results from an average d ecrease in the energy gap. Sequences with large energy gaps support la rger inaccuracies while retaining the ability to fold properly. As the energy gap is known to correlate with thermal stability, we suggest a simple criterion for specific real sequence selection in order to max imize success probability in realistic folding simulations. (C) Curren t Biology Ltd