TY - JOUR

T1 - Thermal unwinding of Polyadenylic·Polyuridylic acid complex with TMPyP4 porphyrin in aqueous solutions

AU - Ivanov, M.

AU - Sizov, V.

AU - Kudrev, A.

PY - 2020/2/15

Y1 - 2020/2/15

N2 - The molecular mechanism of Poly(A)•Poly(U) (Polyadenylic•Polyuridylic acid) polyribonucleotide denaturation was studied through a combination of molecular dynamics (MD) simulations and UV–Vis-melting experiments. UV–Vis absorption spectra of Poly(A)•Poly(U) were measured at different temperatures (20–70 °C) both in the absence and presence of porphyrin-ligand TMPyP4 in equilibrated aqueous solutions (pH 7.0). Thermal behavior of double-stranded structure of Poly(A)•Poly(U) altered by formation of the ternary [Poly(A)•Poly(U)]*(TMPyP4)n complexes was studied with the help of a new semi-soft chemometrics procedure, based on the analyses of fractions of species in solution versus temperature. The melting temperature in the presence of porphyrin is 1.2 °C higher than that for pure polyribonucleotide, which indicates that porphyrin binding contributes to the suppression of transition between the native ordered structure of Poly(A)•Poly(U) and disordered state. MD simulations were performed for the binding of TMPyP4 to (rA)12•(rU)12 oligonucleotide to provide molecular-level insight into the mechanism of duplex dsRNA melting in the presence of TMPyP4. The results of MD simulations suggest a molecular mechanism of thermal stabilization of the native structure through the accommodation of TMPyP4 in double-stranded structure of (rA)12•(rU)12 oligonucleotide groove close to the end of the ordered region of stacked nucleobase pairs.

AB - The molecular mechanism of Poly(A)•Poly(U) (Polyadenylic•Polyuridylic acid) polyribonucleotide denaturation was studied through a combination of molecular dynamics (MD) simulations and UV–Vis-melting experiments. UV–Vis absorption spectra of Poly(A)•Poly(U) were measured at different temperatures (20–70 °C) both in the absence and presence of porphyrin-ligand TMPyP4 in equilibrated aqueous solutions (pH 7.0). Thermal behavior of double-stranded structure of Poly(A)•Poly(U) altered by formation of the ternary [Poly(A)•Poly(U)]*(TMPyP4)n complexes was studied with the help of a new semi-soft chemometrics procedure, based on the analyses of fractions of species in solution versus temperature. The melting temperature in the presence of porphyrin is 1.2 °C higher than that for pure polyribonucleotide, which indicates that porphyrin binding contributes to the suppression of transition between the native ordered structure of Poly(A)•Poly(U) and disordered state. MD simulations were performed for the binding of TMPyP4 to (rA)12•(rU)12 oligonucleotide to provide molecular-level insight into the mechanism of duplex dsRNA melting in the presence of TMPyP4. The results of MD simulations suggest a molecular mechanism of thermal stabilization of the native structure through the accommodation of TMPyP4 in double-stranded structure of (rA)12•(rU)12 oligonucleotide groove close to the end of the ordered region of stacked nucleobase pairs.

KW - Chemometric analysis

KW - Melting

KW - Molecular dynamics simulations

KW - Poly(A)•Poly(U)

KW - TMPyP4

KW - RUTHENIUM(II) POLYPYRIDYL COMPLEX

KW - RNA

KW - MESO-TETRAKIS(N-METHYLPYRIDINIUM-4-YL)PORPHYRIN

KW - Poly(A)center dot Poly(U)

KW - WATER-SOLUBLE PORPHYRINS

KW - LIGANDS

KW - QUADRUPLEX DNA

KW - DYNAMICS

KW - LINEAR CONSTRAINT SOLVER

KW - MOLECULAR LIGHT SWITCH

KW - BINDING

UR - http://www.scopus.com/inward/record.url?scp=85075504316&partnerID=8YFLogxK

UR - http://www.mendeley.com/research/thermal-unwinding-polyadenylicpolyuridylic-acid-complex-tmpyp4-porphyrin-aqueous-solutions

U2 - 10.1016/j.molstruc.2019.127365

DO - 10.1016/j.molstruc.2019.127365

M3 - Article

AN - SCOPUS:85075504316

VL - 1202

JO - Journal of Molecular Structure

JF - Journal of Molecular Structure

SN - 0022-2860

M1 - 127365

ER -