LUTE (Local Unpruned Tuple Expansion): Accurate Continuously Flexible Protein Design with General Energy Functions and Rigid Rotamer-Like Efficiency.


Journal Article

Most protein design algorithms search over discrete conformations and an energy function that is residue-pairwise, that is, 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 such as 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 nonpairwise 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.

Full Text

Cited Authors

  • Hallen, MA; Jou, JD; Donald, BR

Published Date

  • June 2017

Published In

Volume / Issue

  • 24 / 6

Start / End Page

  • 536 - 546

PubMed ID

  • 27681371

Pubmed Central ID

  • 27681371

Electronic International Standard Serial Number (EISSN)

  • 1557-8666

International Standard Serial Number (ISSN)

  • 1066-5277

Digital Object Identifier (DOI)

  • 10.1089/cmb.2016.0136


  • eng