Multiple peptide conformations give rise to similar binding affinities: molecular simulations of p53-MDM2.
Molecular dynamics simulations, guided by experimental information (Zondlo et al. Biochemistry 2006, 45, 11945-11957) have been used successfully to reproduce experimental trends in binding affinities of variant p53 peptides with MDM2. Simulations reveal how the conformations of the peptides and the receptor modulate each other to optimize interactions. The conformations of the uncomplexed peptides are governed by a combination of helix and intrinsic disorder (in agreement with experiments), while in the complexed state two very different conformations can coexist. This yields very similar binding affinities, driven by either enthalpy or entropy.
Dastidar
Shubhra Ghosh
SG
Bioinformatics Institute (A-STAR), 30 Biopolis Street, #07-01 Matrix, Singapore 138671.
Lane
David P
DP
Verma
Chandra S
CS
D003198:Computer Simulation; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D051736:Proto-Oncogene Proteins c-mdm2 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
D010455:Peptides; D016159:Tumor Suppressor Protein p53; D051736:Proto-Oncogene Proteins c-mdm2