LUTE (Local Unpruned Tuple Expansion): Accurate Continuously Flexible Protein Design with General Energy Functions and Rigid-rotamer-like Efficiency
- Cite this paper as:
- Hallen M.A., Jou J.D., Donald B.R. (2016) LUTE (Local Unpruned Tuple Expansion): Accurate Continuously Flexible Protein Design with General Energy Functions and Rigid-rotamer-like Efficiency. In: Singh M. (eds) Research in Computational Molecular Biology. RECOMB 2016. Lecture Notes in Computer Science, vol 9649. Springer, Cham
Most protein design algorithms search over discrete conformations and an energy function that is residue-pairwise, i.e., a sum of terms that depend on the sequence and conformation of at most two residues. Although modeling of continuous flexibility and of non-residue-pairwise energies significantly increases the accuracy of protein design, previous methods to model these phenomena add a significant asymptotic cost to design calculations. We now remove this cost by modeling continuous flexibility and non-residue-pairwise energies in a form suitable for direct input to highly efficient, discrete combinatorial optimization algorithms like DEE/A* or Branch-Width Minimization. Our novel algorithm performs a local unpruned tuple expansion (LUTE), which can efficiently represent both continuous flexibility and general, possibly non-pairwise energy functions to an arbitrary level of accuracy using a discrete energy matrix. We show using 47 design calculation test cases that LUTE provides a dramatic speedup in both single-state and multistate continuously flexible designs.