Guimaraes, Cristiano R. W.; Kopecky, David J.; Mihalic, Jeff; Shen, Shanling; Jeffries, Shawn; Thibault, Stephen T.; Chen, Xiaoqi; Walker, Nigel; Cardozo, Mario published the artcile< Thermodynamic Analysis of mRNA Cap Binding by the Human Initiation Factor eIF4E via Free Energy Perturbations>, Quality Control of 112-63-0, the main research area is mRNA cap translation initiation eIF4E free energy model human.
Eukaryotic mRNAs are appended at the 5′ end, with the 7-methylguanosine cap linked by a 5′-5′-triphosphate bridge to the first transcribed nucleoside (m7GpppX). Initiation of cap-dependent translation of mRNA requires direct interaction between the cap structure and the eukaryotic translation initiation factor eIF4E. Biophys. studies of the association between eIF4E and various cap analogs have demonstrated that m7GTP binds to the protein 閳?5.0 kcal/mol more favorably than unmethylated GTP. In this work, a thermodn. anal. of the binding process between eIF4E and several cap analogs has been conducted using Monte Carlo (MC) simulations in conjunction with free energy perturbation (FEP) calculations To address the role of the 7-Me group in the eIF4E/m7GpppX cap interaction, binding free energies have been computed for m7GTP, GTP, protonated GTP at N(7), the 7-methyldeazaguanosine 5′-triphosphate (m7DTP), and 7-deazaguanosine 5′-triphosphate (DTP) cap analogs. The MC/FEP simulations for the GTP閳姦7DTP transformation demonstrate that half of the binding free energy gain of m7GTP with respect to GTP can be attributed to favorable van der Waals interactions with Trp166 and reduced desolvation penalty due to the N(7) Me group. The Me group both eliminates the desolvation penalty of the N(7) atom upon binding and creates a larger cavity within the solvent that further facilitates the desolvation step. Anal. of the pair m7GTP-m7DTP suggests that the remaining gain in affinity is related to the pos. charge created on the guanine moiety due to the N(7) methylation. The charge provides favorable cation-锜?interactions with Trp56 and Trp102 and decreases the neg. mol. charge, which helps the transfer from the solvent, a more polar environment, to the protein.
Journal of the American Chemical Society published new progress about Cation-pi interaction. 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, Quality Control of 112-63-0.
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