The investigation of the G-quadruplex aptamer selectivity to Pb2+ ion: a joint molecular dynamics simulation and density functional theory study. Issue 12 (12th August 2020)

• Record Type: Journal Article
• Authors: Khoshbin, Zahra; Housaindokht, Mohammad Reza; Izadyar, Mohammad; Bozorgmehr, Mohammad Reza; Verdian, Asma
• Is Part Of: Journal of biomolecular structure & dynamics. Volume 38:Issue 12(2020)
• Page Start: 3659
• Page End: 3675
• Publication Date: 2020-08-12
• Subjects: Molecular dynamics simulation -- quantum mechanics calculation -- aptamer -- G-quadruplex -- aptasensor -- free energy landscape; Biomolecules -- Periodicals; Molecular structure -- Periodicals; Molecular Biology -- Periodicals; Biomechanics -- Periodicals; 572
• DOI: 10.1080/07391102.2019.1664933
• Languages: English
• ISSNs: 0739-1102

Abstract

Abstract: The aptamers with the ability to form a G-quadruplex structure can be stable in the presence of some ions. Hence, study of the interactions between such aptamers and ions can be beneficial to determine the highest selective aptamer toward an ion. In this article, molecular dynamics (MD) simulations and quantum mechanics (QM) calculations have been applied to investigate the selectivity of the T30695 aptamer toward Pb 2+ in comparison with some ions. The Free Energy Landscape (FEL) analysis indicates that Pb 2+ has remained inside the aptamer during the MD simulation, while the other ions have left it. The Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) binding energies prove that the conformational stability of the aptamer is the highest in the presence of Pb 2+ . According to the compaction parameters, the greatest compressed ion-aptamer complex, and hence, the highest ion-aptamer interaction have been induced in the presence of Pb 2+ . The contact maps clarify the closer contacts between the nucleotides of the aptamer in the presence of Pb 2+ . The density functional theory (DFT) results show that Pb 2+ forms the most stable complex with the aptamer, which is consistent with the MD results. The QM calculations reveal that the N-H bonds and the O…H distances are the longest and the shortest, respectively, in the presence of Pb 2+ . The obtained results verify that the strongest hydrogen bonds (HBs), and hence, the most compressed aptamer structure are induced by Pb 2+ . Besides, atoms in molecules (AIM) and natural bond orbital (NBO) analyses confirm the results. Communicated by Ramaswamy H. Sarma