A new approach to the design of a sequence with the highest affinity for a molecular surface

We describe an algorithm to design the primary structures forpeptides which must have the strongest binding to a given molecularsurface. This problem cannot be solved by a direct combinatorialsorting, because of an enormous number of possible primary andspatial structures. The approach to solve this problem is todescribe a state of each residue by two variables: (i) aminoacid type and (ii) 3-D coordinate, and to minimize binding energyover all these variables simultaneously. For short chains whichhave no long-range interactions within themselves, this minimizationcan be done easily and efficiently by dynamic programming. Wealso discuss the problem of how to estimate specificity of bindingand how to deduce a sequence with maximal specificity for agiven surface. We show that this sequence can be deduced bythe same algorithm after some modification of energetic parameters.