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Project/Molecular dynamics and Biology

2. Research plans[Characteristics study of TATA box through comparison of elastic modulus according to DNA sequence]

by sonpang 2021. 11. 11.
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2.1. Introduction

DNA is a field that is very frequently dealt with in the fields of chemistry and life sciences. Then, the question arises, “What are the physical properties of DNA?” “How about studying elasticity, one of the physical properties of DNA, because DNA has a helical structure?” I thought. If we study the elasticity of DNA, we learn that TATA Box (a part with many bonds with two hydrogen bonds in the DNA sequence promoter region) learned in life science class. Also, we found that TATA Box is about 24% in the core promoter of human genes. The part that is generally interpreted as the number of hydrogen bonds can be interpreted in relation to elasticity. This is to be observed using molecular dynamics programs (VMD, NAMD) to observe unwinding in the natural state, and to analyze it using a program called MATLAB through physical modeling.

 

Researchers have found that long molecules that are used to carry genetic information in all living systems are We continue to unravel the surprising properties of DNA. DNA is the most compact known It is a data storage system. By packing all the biological information into such a small space, Wouldn't it be difficult to print or copy?

 

The reason DNA can be so easily accessed by special proteins in cells is that it Because it can be bent without breaking.

 

The elasticity of DNA must be stretched only within a limited range. If it increases too much, The modification may be so severe that an essential protein cannot attach or recognize it. all. If the DNA is too weak, it will break under constant pressure throughout the life of the cell. all.

 

 

2.2. Review of previous research_Theoretical background

DNA helix research and cell characteristics using optical forceps (Professor Yonggu Lee, Nano Simulation Lab, Gwangju Institute of Science and Technology)

Objects that optical forceps (light) can penetrate can be caught with a size of 0.1 to 100 μm, and metal can be caught up to 5 to 100 nm (nanometer, 1 nm = 10-9 m).

광집게(빛)이 침투 할 수 있는 물체는 크기0.1~100μm, 금속은 5~100nm(나노미터, 1nm=10-9m)까지 잡을 수 있다

 

A paper on the elasticity of DNA depending on the valence of ions in a solution containing DNA.

The persistence length of DNA is 250–300 Å when the valence of the ion in the solution containing DNA is 2 or more, and the persistence length of DNA is 450–500 Å when the valence of the ion is 1.

DNA가 들어있는 용액 속 이온의 가수가 2 이상일 때 DNA 의 persistence length는 250–300 Å 이고, 이온의 가수가 1일 때 DNA 의 persistence length는 450–500 Å이다.

 

Physicists at the Institute LaueLangevin (ILL) in Grenoble, France, recently investigated the flexibility of DNA by measuring how well it transmits sound waves. And the results were published in PRL (Physical Review Letters).

In a press release, ILL physicist Mark Johnson said, “We are fundamentally is measuring the speed of sound, which is a direct measure of DNA structural flexibility. provide,” he said.

프랑스 그레노블에 위치한 ILL(Institut LaueLangevin)연구소의 물리학자들은 최근 DNA가 얼마나 잘 음파를 전달하는 지를 측정함으로써 그 유연성(flexibility)을 조사하였다. 그리고 그 결과를 PRL(Physical Review Letters)지에 발표하였다. 보도 자료에서, ILL의 물리학자인 마크 존슨(Mark Johnson)은, ”우리는 DNA에서 근본적으로 소리의 속도를 측정하고 있는 중인데, 그것은 DNA 구조적 유연성의 직접적인 수치를 제공한다”고 말했다.

 

중국과학원 물리연구소 ‘베이징(北京) 응집물질물리 국가 실험실’ 리워이(李偉) 연구원 연구팀과 싱가포르 국립 대학의 옌지에(嚴潔) 교수 연구팀과 협력연구팀

It clarified the effect of DNA reversal elasticity on DNA aggregation and gave scientists a deeper understanding of DNA aggregation in the human body. It was found that a large amount of topoisomerase (releasing a kind of DNA supercoiled enzyme) is present at the binding site of the DNA aggregate and the nuclear matrix of mammalian sperm. Although it is not yet clear what specific role these enzymes play at the binding site, the research team found that the role that these enzymes play at the binding site is related to DNA aggregation and the release of DNA. It implied that the inversion could drive sufficient aggregation of DNA. Related research results were published in the journal Physical Review Letters (Phy. Rev. Lett. 2012, 109 218102).

DNA 반전 탄성이 DNA 응집에 끼치는 영향을 명확히 하였으며 과학자들이 인체 내 DNA 응집에 대해 깊이 이해할 수 있게끔 하였다. DNA 응집체와 포유동물 정자의 핵 매트릭스(Nuclear matrix)의 결합 부위는 대량의 토포이소머라아제(Topoisomerase)(일종 DNA 초나선(Supercoiled) 효소를 방출함)가 존재하고 있다는 점을 발견하였다. 이런 효소가 해당 결합 부위에서 구체적으로 어떤 역할을 발휘하는지에 대해서는 아직 명확한 결론을 내리지는 못하였지만 연구팀은 이번 연구를 통해 이런 효소가 해당 결합 부위에서 발휘하는 역할은 DNA 응집과 관련되며 방출한 DNA의 반전을 통해 DNA의 충분한 응집을 추진할 수 있을 것이라는 점을 암시(Imply)하였다. 관련 연구성과는 Physical Review Letters 학술지에 발표되었다(Phy. Rev. Lett. 2012, 109 218102).

 

 

In the case of optical clippers, it is not at the level where DNA can be grasped down to the level of one strand and studied. Also, in the case of overseas research, it cannot be said to be a direct measurement as it is an indirect measurement.
Therefore, in this study, a more accurate and reliable elastic modulus can be derived by creating a single strand of DNA with an environment suitable for research. In addition, as most of the previous studies were studied to explain the bonding of drugs by examining elasticity, it is different from this study for interpreting the pure science field.

광집게 같은 경우 DNA를 한 가닥 수준까지 잡아 연구 할 수 있는 수준이 아니다. 또한 해외연구의 경우 간접적인 측정으로 직접적인 측정이라 할 수 없다.

따라서 본 연구는 한 가닥을 DNA를 연구에 적합한 환경과 함께 조성하여 조금 더 정확하고 신뢰할 수 있는 탄성계수를 도출할 수 있다. 또한 선행연구는 대부분 탄성을 조사하여 약품 등의 결합을 설명하기 위해 연구된 것임으로 순수 과학 분야를 해석하기 위한 본 연구와는 차이가 있다.

 

 

2.3. B-DNA, A-DNA, Z-DNA_Theoretical background

The double helix structure of DNA includes B-DNA, A-DNA, and Z-DNA. B-DNA: The standard double helix of Watson and Crick, with an overall width of 2.0 nm in DNA, 0.34 nm from one base pair to the next, each base offset by approximately 36 degrees from its adjacent base pair, and a right-turning helix. am. A-DNA: It is wider and shorter than B-DNA, 11 base pairs per helix, and is a right-turning helix. It occurs in RNA or a hybrid of RNA and DNA, or in high-salinity or dehydrated DNA. Z-DNA: Narrower and longer than B-DNA, with 12 base pairs per helix, it is a left-handed helix rather than a right-handed helix. It forms a Z-shaped line rather than a smooth spiral curve, and it is formed at a DNA site where GC or GT base pairs of high salinity DNA alternate a lot.

DNA의 이중나선 구조에는 B-DNA, A-DNA, Z-DNA 가 있다. B-DNA: 왓슨과 크릭의 표준 이중나선으로, DNA의 전체 폭이 2.0nm이고, 한 염기쌍에서 다음 염기쌍까지의 거리는 0.34nm이며, 각 염기가 인접한 염기쌍과 약 36도씩 빗겨나 놓여 있고, 우회전 나선이다. A-DNA: B-DNA보다 폭이 더 넓고 길이가 더 짧으며 나선 한 회전 당 11염기쌍을 가지고, 우회전 나선이다.RNA또는 RNA와 DNA의 혼성분자, 또는 고염도나 탈수되었을 때의 DNA에서 나타난다. Z-DNA: B-DNA보다 폭이 더 좁고 길며 나선 1회전 당 12 염기쌍을 가지고, 우회전 나선이 아니라 좌회전 나선이다. 부드러운 나선 곡선 보다는 Z형의 선을 형성하며, 고염도에 있는 DNA의 GC혹은 GT 염기쌍이 많이 교대되는 DNA 부위에서 형성된다.

 

 

2.4. Research

In general, the number of hydrogen bonds according to the presence of the TATA box in the promoter region explains the degree of ease of DNA unwinding. I will try to explain this physically. The elastic modulus of the TATA Box is studied by setting the breakage of hydrogen bonds between bases as the elastic limit. Study the elasticity (according to the base composition) of RNA and DNA. Through this, it will be possible to explore the modulus of elasticity (parallel * series connection) in the microscopic world. We will also examine how hydrogen bonding in DNA affects elasticity.

 

DNA elasticity according to temperature

DNA, RNA elasticity

Elasticity according to the type of DNA

 

① DNA is formed using VMD, a molecular visualization program that displays and analyzes large biomolecular systems with 3D graphics.

② Set the files necessary for the simulation, and perform the simulation through NAMD (simulation of large-scale biomolecular system).

③ Model for physical analysis.

④ Write MATLAB code based on modeling.

⑤ Analyze the results obtained through MATLAB and find ways to use it.

 

 

2.5. Expected results

  • We will be able to derive a value corresponding to the modulus of elasticity.
  • It will be possible to physically explain the characteristics of the TATA Box.
  • We will be able to know the physical properties (elasticity) of DNA and RNA.

 

 

2.6. Reference

Ionic effects on the elasticity of single DNA molecules-Christoph G. Baumann*, Steven B. Smith†, Victor A. Bloomfield*, and Carlos Bustamante

*Department of Biochemistry, University of Minnesota, St. Paul, MN 55108; and †Institute of Molecular Biology and Department of Chemistry

and ‡Howard Hughes Medical Institute, University of Oregon, Eugene, OR 97403

Communicated by Brian W. Matthews, University of Oregon, Eugene, OR, April 7, 1997 (received for review February 4, 1997)

 

설계를 가리키는 DNA의 유연성(한국창조과학회, Design in DNA: Flexibility Is Just Right)

David P. Clark & Nanette J.Pazdernik, 분자생물학, 113, 114, 115 (월드사이언스, 2014)

유전공학의 이해 3판 남상욱 (라이프사이언스, 2016.09.01)

한국연구재단 [NT] 나노물질 시뮬레이션 기술(국가나노기술정책센터)

VDNA: The virtual DNA plug-in for VMD Thomas C. Bishop(Bioinformatics, 2009 3187-3188.)

 

Reference material for PDB file composition study

http://www.ks.uiuc.edu/ (Beckman Institute for Advanced Science and Technology // National Institutes of Health // National Science Foundation // Physics, Computer Science, and Biophysics at University of Illinois at Urbana-Champaign)

http://www.rcsb.org/ (Protein Data Bank (PDB) 기록 보관소,RCSB PDB Advisory Committee, Research Collaboratory for Structural Bioinformatics Protein Data Bank)

http://www.wwpdb.org/ (자연 구조 생물학 연구, Since 1971, the Protein Data Bank archive (PDB))

http://www.ebi.ac.uk/pdbe/ (Protein Data Bank in Europe)

http://pdbj.org/ (Protein Data Bank Japan)

http://www.bmrb.wisc.edu/ (Biological Magnetic Resonance Data Bank)

http://www.fluortools.com/misc/scientific-illustration/w3dna

 

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