Comets (Constrained Optimization of Multistate Energies by Tree Search): A Provable and Efficient Algorithm to Optimize Binding Affinity and Specificity with Respect to Sequence

  • Mark A. Hallen
  • Bruce R. DonaldEmail author
Conference paper
Part of the Lecture Notes in Computer Science book series (LNCS, volume 9029)


Practical protein design problems require designing sequences with a combination of affinity, stability, and specificity requirements. Multistate protein design algorithms model multiple structural or binding “states" of a protein to address these requirements. comets provides a new level of versatile, efficient, and provable multistate design. It provably returns the minimum with respect to sequence of any desired linear combination of the energies of multiple protein states, subject to constraints on other linear combinations. Thus, it can target nearly any combination of affinity (to one or multiple ligands), specificity, and stability (for multiple states if needed). Empirical calculations on 52 protein design problems showed comets is far more efficient than the previous state of the art for provable multistate design (exhaustive search over sequences). comets can handle a very wide range of protein flexibility and can enumerate a gap-free list of the best constraint-satisfying sequences in order of objective function value.


Protein Design Sequence Space Exhaustive Search Conformational Space Unbind State 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Department of Computer ScienceDuke UniversityDurhamUSA
  2. 2.Department of BiochemistryDuke University Medical CenterDurhamUSA

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