Applying Constraint Programming to Rigid Body Protein Docking

In this paper we show how Constraint Programming (CP) techniques can improve the efficiency and applicability of grid-based algorithms for optimising surface contact between complex solids. We use BiGGER [1] (Bimolecular complex Generation with Global Evaluation and Ranking) to illustrate the method as applied to modelling protein interactions, an important effort in current bioinformatics. BiGGER prunes the search space by maintaining bounds consistency on interval constraints that model the requirement for the shapes to be in contact but not overlapping, and by using a branch and bound approach to search the models with the best fit. This CP approach gives BiGGER some efficiency advantages over popular protein docking methods that use Fourier transforms to match protein structures. We also present an efficient algorithm to actively impose a broad range of constraints or combinations of constraints on distances between points of the two structures to dock, which allows the use of experimental data to increase the effectiveness and speed of modelling protein interactions and which cannot be done as efficiently in Fourier transform methods. This shows that constraint programming provides a different approach to protein docking (and fitting of shapes in general) that increases the scope of application while improving efficiency.