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A free energy analysis by unfolding applied to 125-mers on a cubic lattice
M S Chung1, A F Neuwald, W J Wilbur
1National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA.
Background:
A common approach to the protein folding problem involves computer simulation of folding using lattice models of amino acid sequences. Key factors for good performance in such models are the correct choice of the temperature and the average interaction energy between residues. In order to push the lattice approach to its limit it is important to have a method to adjust these parameters for optimal folding that is not limited by our ability to successfully simulate folding in a reasonable time.
Results:
In this study, we adopt a simple cubic-lattice model and present a method for calculating the free energy of a chain as a function of the number of native contacts. This does not require that we are able to fold the sequence by simulation and it provides a method of estimating the folding transition temperature. For a given set of parameters, the free energy analysis also allows an estimate of foldability. By applying the method to sequences with 27 and 125 residues, we show that optimal folding occurs near the folding transition temperature and at either zero or small negative average interaction energy. We find ourselves able to fold only 125-mers that have significant short-range native contacts.
Conclusions:
A free energy analysis during unfolding is a useful tool for the study of foldability and should be applicable to a variety of folding models. In this way we are able to fold some 125-mer designed sequences and our results confirm the finding that short-range contacts contribute to foldability.