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Mandar KulkarniMandar Kulkarni

부산대학교

Nucleic Acids Res., Published: 03 November 2017 | https://doi.org/10.1093/nar/gkx1079 In silico direct folding of thrombin-binding aptamer G-quadruplex at all-atom level

Changwon Yang^†, Mandar Kulkarni^†, Manho Lim and Youngshang Pak^*

Department of Chemistry and Institute of Functional Materials, Pusan National University, Busan 609-735, South Korea

^*To whom correspondence should be addressed.
^†These authors contributed equally to the paper as first authors.

Present address: Prof. Youngshang Pak, Department of Chemistry and Institute of Functional Materials, Pusan National University, Busan 609-735, South Korea

Abstract

The reversible folding of the thrombin-binding DNA aptamer G-quadruplexes (GQs) (TBA-15) starting from fully unfolded states was demonstrated using a prolonged time scale (10-12 μs) parallel tempering metadynamics (PTMetaD) simulation method in conjunction with a modified version of the AMBER bsc1 force field. For unbiased descriptions of the folding free energy landscape of TBA-15, this force field was minimally modified. From this direct folding simulation using the modified bsc1 force field, reasonably converged free energy landscapes were obtained in K⁺-rich aqueous solution (150 mM), providing detailed atomistic pictures of GQ folding mechanisms for TBA-15. This study found that the TBA folding occurred via multiple folding pathways with two major free energy barriers of 13 and 15 kcal/mol in the presence of several intermediate states of G-triplex variants. The early formation of these intermediates was associated with a single K⁺ ion capturing. Interestingly, these intermediate states appear to undergo facile transitions among themselves through relatively small energy barriers.

논문정보

형식Research article
게재일2017년 11월 (BRIC 등록일 2017-11-17)
연구진국내 연구진
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