PMID- 38170800
OWN - NLM
STAT- MEDLINE
DCOM- 20240118
LR  - 20240206
IS  - 1463-9084 (Electronic)
IS  - 1463-9076 (Linking)
VI  - 26
IP  - 3
DP  - 2024 Jan 17
TI  - Probing the conformational dynamics of an Ago-RNA complex in water/methanol 
      solution.
PG  - 2497-2508
LID - 10.1039/d3cp05530b [doi]
AB  - Argonaute (Ago) proteins mediate target recognition guiding miRNA to bind 
      complementary mRNA primarily in the seed region. However, additional pairing can 
      occur beyond the seed, forming a supplementary duplex that can contribute to the 
      guide-target affinity. In order to shed light on the connection, between 
      protein-RNA interactions and miRNA-mRNA seed and supplementary duplex mobility, 
      we carried out molecular dynamics simulations at the microsecond time-scale using 
      a different approach compared to the ones normally used. Until now, theoretical 
      investigations with classical MD on Ago-RNA complexes have been focused primarily 
      on pure water solvent, which mimics the natural environment of biological 
      molecules. Here, we explored the conformational space of a human Ago2 (hAgo2) 
      bound to the seed + supplementary miRNA-mRNA duplex, using the solvent 
      environment as a molecular probe. MD simulations have been performed in a mixture 
      of water/MeOH at a molar ratio of 70 : 30 as well as in pure water for 
      comparison. Our findings revealed that the mixed solvent promotes protein RNA 
      association, principally enhancing salt-linkages between basic amino acid 
      side-chains and acidic phosphates of the sugar-phosphate backbone. The primary 
      effect registered was the restriction of supplementary duplex flexibility and the 
      stabilization of the miRNA 3' terminus. Interestingly, we observed that the 
      influence of the solvent appears to have almost no impact on the conformation of 
      the seed duplex.
FAU - Porcelli, Francesco
AU  - Porcelli F
AUID- ORCID: 0000-0001-6032-2691
AD  - CNR-Istituto di Struttura della Materia, Area della Ricerca di Roma 1, CP 10 
      Monterotondo Scalo, Italy. Francesco.Porcelli@mlib.ism.cnr.it.
FAU - Casavola, Anna Rita
AU  - Casavola AR
AD  - CNR-Istituto di Struttura della Materia, Area della Ricerca di Roma 1, CP 10 
      Monterotondo Scalo, Italy. Francesco.Porcelli@mlib.ism.cnr.it.
FAU - Grottesi, Alessandro
AU  - Grottesi A
AD  - Cineca, Via dei Tizii, 6, Rome, Italy.
FAU - Schiumarini, Donatella
AU  - Schiumarini D
AD  - CNR-Istituto di Struttura della Materia, Area della Ricerca di Roma 1, CP 10 
      Monterotondo Scalo, Italy. Francesco.Porcelli@mlib.ism.cnr.it.
FAU - Avaldi, Lorenzo
AU  - Avaldi L
AUID- ORCID: 0000-0002-2990-7330
AD  - CNR-Istituto di Struttura della Materia, Area della Ricerca di Roma 1, CP 10 
      Monterotondo Scalo, Italy. Francesco.Porcelli@mlib.ism.cnr.it.
LA  - eng
PT  - Journal Article
DEP - 20240117
PL  - England
TA  - Phys Chem Chem Phys
JT  - Physical chemistry chemical physics : PCCP
JID - 100888160
RN  - Y4S76JWI15 (Methanol)
RN  - 0 (MicroRNAs)
RN  - 0 (RNA, Messenger)
RN  - 0 (Solvents)
SB  - IM
MH  - Humans
MH  - *Methanol
MH  - Protein Binding
MH  - *MicroRNAs/chemistry
MH  - RNA, Messenger/chemistry
MH  - Solvents
EDAT- 2024/01/04 01:18
MHDA- 2024/01/18 06:43
CRDT- 2024/01/03 14:13
PHST- 2024/01/18 06:43 [medline]
PHST- 2024/01/04 01:18 [pubmed]
PHST- 2024/01/03 14:13 [entrez]
AID - 10.1039/d3cp05530b [doi]
PST - epublish
SO  - Phys Chem Chem Phys. 2024 Jan 17;26(3):2497-2508. doi: 10.1039/d3cp05530b.