The cis and trans conformations of the Xaa-Pro (Xaa: any amino acid) peptide bond are thermodynamically stable while other peptide bonds strongly prefer trans. The effect of proline cis-trans isomerization on protein binding has not been thoroughly investigated. In this study, computer simulations were used to calculate the absolute binding affinity for a p53 peptide (residues 17-29) to MDM2 for both cis and trans isomers of the p53 proline in position 27. Results show that the cis isomer of p53(17-29) binds more weakly to MDM2 than the trans isomer, and that this is primarily due to the difference in the free energy cost associated with the loss of conformational entropy of p53(17-29) when it binds to MDM2. The stronger binding of trans p53(17-29) to MDM2 compared to cis may leave a minimal level of p53 available to respond to cellular stress. The population of cis p53(17-29) was estimated to be 0.8% of the total population in the bound state. This study demonstrates that it is feasible to estimate the absolute binding affinity for an intrinsically disordered protein fragment binding to an ordered protein that are in good agreement with experimental results.
This research output has an Altmetric Attention Score of 8. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 25 November 2021.
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#6,491,360
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#1,119
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Outputs of similar age from Archives of Biochemistry & Biophysics
#7
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Altmetric has tracked 34,363,559 research outputs across all sources so far. Compared to these this one has done well and is in the 80th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 7,892 research outputs from this source. They receive a mean Attention Score of 4.7. This one has done well, scoring higher than 85% of its peers.
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We're also able to compare this research output to 40 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 82% of its contemporaries.
