Prediction of the interaction between spermidine and the G-G mismatch containing acceptor stem in tRNA(Ile): molecular modeling, density functional theory, and molecular dynamics study.
Polyamines, putrescine, spermidine (SPD), and spermine are closely linked to cell growth, and highly regulate the levels of transcription, translation and protein turnover. We propose that SPD stimulates the formation of Ile-tRNA(Ile) by inducing a selective structural change of the G-G mismatch containing acceptor stem in tRNA(Ile). Here, we provide insight into how SPD recognizes and stabilizes the G-G mismatch containing acceptor stem in tRNA(Ile) with molecular modeling (MM), density functional theory (DFT) calculations, and molecular dynamics (MD) simulations. The results of the MM and DFT calculations indicate that the negatively charged region of the G-G mismatch containing acceptor stem in tRNA(Ile) is preferentially recognized by positively charged SPD. In addition, MD simulations indicate that all of the positively charged amino groups of SPD under physiological conditions (N1(NH3(+)), N5(NH2(+)), and N10(NH3(+)) could form hydrogen bonds with tRNA(Ile) and trigger the SPD-induced stabilization and structural change of the G-G mismatch containing acceptor stem in tRNA(Ile). Thus, this approach should be useful for determining the preferential binding site and appropriate binding mode of polyamines on tRNA(Ile).
Department of Organic and Polymeric Materials, Graduate School of Science and Engineering, Tokyo Institute of Technology, Tokyo 152-8522, Japan.
Yoshihiro
Y
Hayashi
Hajime
H
Sugiyama
Akiko
A
Suganami
Kyohei
K
Higashi
Keiko
K
Kashiwagi
Kazuei
K
Igarashi
Susumu
S
Kawauchi
Yutaka
Y
Tamura
D020137:Base Pair Mismatch; D001665:Binding Sites; D003198:Computer Simulation; D006860:Hydrogen Bonding; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D012355:RNA, Transfer, Ile / Q000737:chemistry* / Q000235:genetics; D013095:Spermidine / Q000737:chemistry*
D012355:RNA, Transfer, Ile; D013095:Spermidine
DFT; Density functional theory; MD; MM; Molecular dynamics simulations; Polyamine; SPD; Spermidine; density functional theory; molecular dynamics; molecular modeling; spermidine; tRNA