Determination of interaction potentials of amino acids from native proteinstructures: Tests on simple lattice models

We propose a novel method for the determination of the effective interactio n potential between the amino acids of a protein. The strategy is based on the combination of a new optimization procedure and a geometrical argument, which also uncovers the shortcomings of any optimization scheme. The strat egy can be applied on any data set of native structures such as those avail able from the Protein Data Bank. In this work, however, we explain and test our approach on simple lattice models, where the true interactions are kno wn a priori and a Model Protein Data Bank (MPDB) can be generated by identi fying proteins as amino acid sequences having a unique ground state conform ation among all possible conformations. Excellent agreement is obtained bet ween the extracted and the true potentials even for modest numbers of prote in structures in the MPDB. Comparisons with other methods are also discusse d. (C) 1999 American Institute of Physics. [S0021-9606(99)50319-X].