LUTE ( Local Unpruned Tuple Expansion ) : Accurate continuously flexible protein design with general energy functions and rigid - rotamer - like e � ciency Supplementary Information

Section A describes the least-squares method used to calculate the LUTE matrix. Section B describes what terms need to be included in the energy matrix. Each term corresponds to a tuple of RCs at di↵erent positions. Section C describes how a pruning interval, a parameter used for pruning in continuously flexible designs, can be computed for several types of LUTE calculations. Section D provides further details of our implementation of LUTE combined with the iMinDEE [Gainza et al., 2012] algorithm for sequence and conformational search. Section E analyzes the complexity of LUTE combined with the BWM⇤ algorithm for sequence and conformational search. It includes a proof of Theorem 3.1. Section F presents novel pruning algorithms that we have developed to solve some of the larger continuously flexible designs that LUTE has made possible. Section G provides details of the protein design test cases described in Section 3.