Computational protein design energy function

We have recently introduced a combined structural, computational, and experimental approach for the de novo design of novel inhibitors such as variants of the synthetic cyclic peptide Compstatin. A novel two-stage computational protein design method is used not only to select and rank sequences for a particular fold but also to validate the stability of the fold for these selected sequences. To correctly select a sequence compatible with a given backbone template that is flexible and represented by several NMR structures, an appropriate energy function must first be identified. The proposed sequence selection procedure is based on optimizing a pairwise distance-dependent interaction potential. A number of different parameterizations for pairwise residue interaction potentials exist the one employed here is based on the discretization of alpha carbon distances into a set of 13 bins to create a finite number of interactions, the parameters of which were derived from a linear optimization formulated to favor native folds over... 

Furthermore, yet to be computed by any program is the fundamental thermo-mechanical transduction wherein the cross-linked elastic-contractile model proteins contract and perform mechanical work on raising the temperature through their respective inverse temperature transitions. These results first appeared in the literature in 1986 and have repeatedly appeared since that time with different preparations, compositions, and experimental characterizations. Additionally, the set of energies converted by moving the temperature of the inverse temperature transition (as the result of input energies for which the elastic-contractile model protein has been designed to be responsive) have yet to be described by computations routinely used to explain protein structure and function. 

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