Structural Analysis of α-Fetoprotein (AFP)-like Peptides with Anti-Breast-Cancer Properties
ACS Citation
Temelso, B.; Alser, K. A.; Gauthier, A.; Palmer, A. K.; Shields, G. C. Structural Analysis of α-Fetoprotein (AFP)-like Peptides with Anti-Breast-Cancer Properties. J. Phys. Chem. B 2014, 118 (17), 4514-4526.
Version of Record
Abstract
The abundance of α-fetoprotein (AFP), a natural protein produced by the fetal yolk sac during pregnancy, correlates with lower incidence of estrogen receptor positive (ER+) breast cancer. The pharmacophore region of AFP has been narrowed down to a four amino acid (AA) region in the third domain of the 591 AA peptide. Our computational study focuses on a 4-mer segment consisting of the amino acids threonine-proline-valine-asparagine (TPVN). We have run replica exchange molecular dynamics (REMD) simulations and used 120 configurational snapshots from the total trajectory as starting configurations for quantum chemical calculations. We optimized structures using semiempirical (PM3, PM6, PM6-D2, PM6-H2, PM6-DH+, PM6-DH2) and density functional methods (TPSS, PBE0, M06-2X). By comparing the accuracy of these methods against RI-MP2 benchmarks, we devised a protocol for calculating the lowest energy conformers of these peptides accurately and efficiently.
Source Name
The Journal of Physical Chemistry B
Publication Date
2014
Volume
118
Issue
17
Page(s)
4514-4526
Document Type
Citation
Citation Type
Article