“生物分子在納通道中的輸運(yùn)及調(diào)控”年度報(bào)告

胡國慶++崔樹勛

摘 要：為了實(shí)現(xiàn)基于納米孔的低成本超快速DNA測(cè)序，需要研究受限空間內(nèi)聚合物分子的構(gòu)象機(jī)制、摩擦特性，同時(shí)要發(fā)展流體動(dòng)力學(xué)模型以描述受限空間內(nèi)生物分子的輸運(yùn)規(guī)律。在該年度，我們進(jìn)一步發(fā)展了粗粒化分子動(dòng)力學(xué)模擬模型，開展跨尺度流體動(dòng)力學(xué)建模和計(jì)算，并且利用單分子力譜直接探測(cè)DNA的單分子界面摩擦力。主要研究結(jié)果如下：對(duì)DNA分子在石墨烯納孔和氧化石墨烯納孔中的穿孔過程進(jìn)行了研究，發(fā)現(xiàn)氧化石墨烯納孔有可能實(shí)現(xiàn)單鏈DNA分子的逐個(gè)堿基過孔；實(shí)驗(yàn)研究了多價(jià)離子溶液中的納孔振蕩電流信號(hào)、離子在納尺度受限空間中的擴(kuò)散系數(shù)以及低濃度下表面電荷平衡過程對(duì)擴(kuò)散的影響，獲得了多個(gè)重要結(jié)果；進(jìn)行了納米顆粒的過孔實(shí)驗(yàn)，獲得顆粒過孔信號(hào)，同時(shí)發(fā)展了能更準(zhǔn)確地預(yù)測(cè)納孔介入電阻的理論模型；測(cè)量了不同NaCl濃度下DNA的摩擦行為，發(fā)現(xiàn)隨著濃度增加，DNA摩擦力減少，而DNA在低濃度下顯示出較為舒展的構(gòu)象；發(fā)現(xiàn)長鏈DNA分子具有更舒展的構(gòu)象，同時(shí)鏈長對(duì)DNA摩擦力的影響不大；單分子力譜研究表明，雙鏈DNA在重水和普通水緩沖溶液中的力學(xué)穩(wěn)定性無顯著性差異，而雙鏈DNA在甲醇中會(huì)自動(dòng)解螺旋，形成單鏈DNA。這些研究將加深我們對(duì)于DNA等生物分子在受限空間內(nèi)受力的科學(xué)認(rèn)識(shí)，為DNA分子過孔測(cè)序技術(shù)的發(fā)展提供理論依據(jù)和設(shè)計(jì)指導(dǎo)。

關(guān)鍵詞：納米孔 DNA 粗粒化 摩擦力

Annual Report of “Transport and Manipulation of Biomolecules in Nanochannels”

Hu Guoqing1 Cui Shuxun2

（1.Institute of Mechanics， Chinese Academy of Sciences； 2.Southwest Jiaotong University）

Abstract： To realize the nanopore-based low cost ultrafast DNA sequencing， it is necessary to investigate the conformation and friction behaviors of polymer and to develop fluid dynamic model to describe the transport of biomolecules in confined space. This year， we further developed the coarse-grained molecular dynamics simulation model to carry out the multiscale modeling and computing of fluid dynamics. The single-molecule interface friction of DNA was directly probed using the single-molecule force spectroscopy. The main results are as follows： The study of the translocation of DNA through graphene nanpore and graphene-oxide nanpore reveals that it is possible to achieve the base-by-base DNA translocation through the graphene-oxide nanopore； Experiments were conducted to investigate the oscillation of nanpore currents in multi-valence solution， diffusion of ions in confined nanochannel and its dependence on surface charge equilibrium， resulting in several important findings； The particle translocation was detected by experimentally measuring the ionic current. Meanwhile， a theoretical model was proposed to predict the access resistance of nanopores； The measurement of fiction of DNA in different NaCl concentrations revealed that DNA friction decreases with the increasing of salt concentration and DNA displays more extended conformation under low salt concentration； It was also found that the long DNA molecule has more extended conformation and the friction is insensitive to the DNA length； The measurements by the single-molecule force spectroscopy showed that the double-stranded DNA has similar dynamic stability in both heavy water and water buffers. However， the double-stranded DNA in methanol will de-helix to form single-stranded DNA. These studies will extend our understanding of forces acting on DNA and other biomolecules in the confined space and provide a theoretical basis and design guide for the development of DNA sequencing techniques.

Key Words： Nanopore； DNA； Coarse grained； Friction

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