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Flex ddG: Rosetta Ensemble-Based Estimation of Changes in Protein–Protein Binding Affinity upon Mutation

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Barlow, Kyle A., Ó Conchúir, Shane, Thompson, Samuel, Suresh, Pooja, Lucas, James E., Heinonen, Markus, Kortemme, Tanja·2018·The Journal of Physical Chemistry B
DOI 10.1021/acs.jpcb.7b11367

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Abstract

Computationally modeling changes in binding free energies upon mutation (interface ΔΔ G) allows large-scale prediction and perturbation of protein-protein interactions. Additionally, methods that consider and sample relevant conformational plasticity should be able to achieve higher prediction accuracy over methods that do not. To test this hypothesis, we developed a method within the Rosetta macromolecular modeling suite (flex ddG) that samples conformational diversity using "backrub" to generate an ensemble of models and then applies torsion minimization, side chain repacking, and averaging across this ensemble to estimate interface ΔΔ G values. We tested our method on a curated benchmark set of 1240 mutants, and found the method outperformed existing methods that sampled conformational space to a lesser degree. We observed considerable improvements with flex ddG over existing methods on the subset of small side chain to large side chain mutations, as well as for multiple simultaneous non-alanine mutations, stabilizing mutations, and mutations in antibody-antigen interfaces. Finally, we applied a generalized additive model (GAM) approach to the Rosetta energy function; the resulting nonlinear reweighting model improved the agreement with experimentally determined interface ΔΔ G values but also highlighted the necessity of future energy function improvements.

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Research works printed but not linked: 49

  1. 10.1016/j.pbiomolbio.2016.10.002 · DOI
  2. 10.1002/prot.22894 · DOI
  3. 10.1093/nar/gkt450 · DOI · Paper page
  4. 10.1021/ct400295z · DOI
  5. 10.7554/eLife.07454 · DOI
  6. 10.1093/bioinformatics/btp240 · DOI
  7. 10.1093/bioinformatics/btt691 · DOI · Paper page
  8. 10.1002/prot.23094 · DOI
  9. 10.1038/nchembio.251 · DOI
  10. 10.1021/bi902153g · DOI · Paper page
  11. 10.1016/S1097-2765(03)00365-4 · DOI
  12. 10.1016/S0969-2126(03)00047-9 · DOI
  13. 10.1016/j.jmb.2007.05.096 · DOI
  14. 10.1074/jbc.M510454200 · DOI
  15. 10.1073/pnas.1114487109 · DOI
  16. 10.1016/S1097-2765(02)00690-1 · DOI
  17. 10.1002/prot.22921 · DOI
  18. 10.1073/pnas.202485799 · DOI · Paper page
  19. 10.1126/stke.2192004pl2 · DOI · Paper page
  20. 10.1371/journal.pone.0130433 · DOI
  21. 10.1126/science.2471267 · DOI · Paper page
  22. 10.1016/j.str.2015.07.021 · DOI
  23. 10.1021/acs.jcim.6b00398 · DOI
  24. 10.1016/j.jmb.2008.05.023 · DOI
  25. 10.1016/j.str.2005.10.007 · DOI · Paper page
  26. 10.1371/journal.pcbi.1002629 · DOI
  27. 10.1016/j.jmb.2008.05.006 · DOI
  28. 10.1016/j.str.2008.09.012 · DOI
  29. 10.1016/j.jmb.2010.07.032 · DOI
  30. 10.1371/journal.pone.0020451 · DOI
  31. 10.1093/bioinformatics/btw001 · DOI
  32. 10.1371/journal.pcbi.1004335 · DOI
  33. 10.1002/prot.24457 · DOI
  34. Simpson R. J., 2002, Proteins and Proteomics: A Laboratory Manual
  35. 10.1093/nar/gkt1043 · DOI · Paper page
  36. 10.1371/journal.pone.0020161 · DOI · Paper page
  37. 10.1371/journal.pone.0020937 · DOI
  38. 10.1002/prot.23013 · DOI
  39. 10.1021/ct500864r · DOI
  40. 10.1002/(SICI)1097-0134(19990501)35:2<133::AID-PROT1>3.0.CO;2-N · DOI
  41. 10.1016/S0022-2836(03)00021-4 · DOI
  42. Hastie T. J., 1990, Generalized Additive Models
  43. 10.1016/j.str.2013.10.019 · DOI
  44. 10.1002/pro.2618 · DOI
  45. 10.1093/nar/gkq1105 · DOI · Paper page
  46. 10.1016/B978-0-12-394292-0.00006-0 · DOI
  47. 10.1016/j.str.2017.09.002 · DOI
  48. 10.1002/prot.20786 · DOI
  49. 10.1002/pro.3317 · DOI

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Metadata

Authors
Barlow, K. A., Ó Conchúir, S., Thompson, S., Suresh, P., Lucas, J. E., Heinonen, M., & Kortemme, T.
Venue
The Journal of Physical Chemistry B
Publisher
American Chemical Society (ACS)
Published
2018-02-05
Volume
122
Issue
21
Pages
5389-5399
ISSN
  • 1520-5207 (ISSN-L)
  • 1520-6106
DOI
10.1021/acs.jpcb.7b11367
OpenAlex
W2780523853
Cited by
295
References
12
FWCI
6.36
Type
journal article
Language
en
Open access
green
Funders
  • Suomen Akatemia (299915)
  • National Institute of General Medical Sciences (R01 GM110089, R01 GM117189)
  • National Science Foundation

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CoChat. (2026). Citation check: Flex ddG: Rosetta Ensemble-Based Estimation of Changes in Protein–Protein Binding Affinity upon Mutation. https://app.cochat.ai/papers/10.1021/acs.jpcb.7b11367
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Barlow, K. A., Ó Conchúir, S., Thompson, S., Suresh, P., Lucas, J. E., Heinonen, M., & Kortemme, T. (2018). Flex ddG: Rosetta Ensemble-Based Estimation of Changes in Protein–Protein Binding Affinity upon Mutation. The Journal of Physical Chemistry B. https://doi.org/10.1021/acs.jpcb.7b11367

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