Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Community-wide assessment of protein-interface modeling suggests improvements to design methodology.

Fleishman SJ | Whitehead TA | Strauch EM | Corn JE | Qin S | Zhou HX | Mitchell JC | Demerdash ON | Takeda-Shitaka M | Terashi G | Moal IH | Li X | Bates PA | Zacharias M | Park H | Ko JS | Lee H | Seok C | Bourquard T | Bernauer J | Poupon A | Azé J | Soner S | Ovali SK | Ozbek P | Tal NB | Haliloglu T | Hwang H | Vreven T | Pierce BG | Weng Z | Pérez-Cano L | Pons C | Fernández-Recio J | Jiang F | Yang F | Gong X | Cao L | Xu X | Liu B | Wang P | Li C | Wang C | Robert CH | Guharoy M | Liu S | Huang Y | Li L | Guo D | Chen Y | Xiao Y | London N | Itzhaki Z | Schueler-Furman O | Inbar Y | Potapov V | Cohen M | Schreiber G | Tsuchiya Y | Kanamori E | Standley DM | Nakamura H | Kinoshita K | Driggers CM | Hall RG | Morgan JL | Hsu VL | Zhan J | Yang Y | Zhou Y | Kastritis PL | Bonvin AM | Zhang W | Camacho CJ | Kilambi KP | Sircar A | Gray JJ | Ohue M | Uchikoga N | Matsuzaki Y | Ishida T | Akiyama Y | Khashan R | Bush S | Fouches D | Tropsha A | Esquivel-Rodríguez J | Kihara D | Stranges PB | Jacak R | Kuhlman B | Huang SY | Zou X | Wodak SJ | Janin J | Baker D

http://www.ncbi.nlm.nih.gov/pubmed/22001016

The CAPRI (Critical Assessment of Predicted Interactions) and CASP (Critical Assessment of protein Structure Prediction) experiments have demonstrated the power of community-wide tests of methodology in assessing the current state of the art and spurring progress in the very challenging areas of protein docking and structure prediction. We sought to bring the power of community-wide experiments to bear on a very challenging protein design problem that provides a complementary but equally fundamental test of current understanding of protein-binding thermodynamics. We have generated a number of designed protein-protein interfaces with very favorable computed binding energies but which do not appear to be formed in experiments, suggesting that there may be important physical chemistry missing in the energy calculations. A total of 28 research groups took up the challenge of determining what is missing: we provided structures of 87 designed complexes and 120 naturally occurring complexes and asked participants to identify energetic contributions and/or structural features that distinguish between the two sets. The community found that electrostatics and solvation terms partially distinguish the designs from the natural complexes, largely due to the nonpolar character of the designed interactions. Beyond this polarity difference, the community found that the designed binding surfaces were, on average, structurally less embedded in the designed monomers, suggesting that backbone conformational rigidity at the designed surface is important for realization of the designed function. These results can be used to improve computational design strategies, but there is still much to be learned; for example, one designed complex, which does form in experiments, was classified by all metrics as a nonbinder.

Pubmed ID: 22001016 RIS Download

Mesh terms: Binding Sites | Models, Molecular | Protein Binding | Proteins

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: NCRR NIH HHS, Id: P41 RR011823
  • Agency: NIGMS NIH HHS, Id: R01 GM073960
  • Agency: NIGMS NIH HHS, Id: R01 GM078221
  • Agency: NIGMS NIH HHS, Id: R01 GM084884
  • Agency: Canadian Institutes of Health Research, Id:
  • Agency: Howard Hughes Medical Institute, Id:

Addgene (Reagent, Plasmid)

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.