First-principles Studies On The Properties Of DNA And Its Interactions With Carcinogenic Small Organic Molecules

In the past century,quantum mechanics' development has greatly deepened peo-ple's understanding of nature's laws.However,the computational complexity of quan-tum mechanics has long limited its application.In recent decades,first-principles method based on density functional theory(DFT)has been continuously developed.With the rapid advancement of computer hardware technology and software algorithms,the first-principles method can handle a bigger and bigger system,and its calculation accuracy continues to increase.It has been applied in condensed matter physics,chem-istry,biology,and materials science and has made remarkable successes,making it a more and more popular research method in these fields.DNA is a star molecule in biology as genetic material,and its structural and other properties have always attracted people's attention.The study of DNA has answered many questions in the field of biology.Besides,DNA is also a promising research object in the field of materials science.Further research on the structural and other properties of DNA will significantly promote the development of related fields.In addition,DNA is also a vital molecule in the occurrence and development of cancer.Cancer is an important disease facing human beings.Studying the interaction between DNA and carcinogens is of great significance for understanding cancer and treating cancer.However,as a biological macromolecule,DNA has considerable complexity.The more profoundly people study DNA,the more this complexity is revealed.For exam-ple,at first,people only discovered two configurations of DNA,but as research contin-ues,new configurations have been discovered,and now more than ten configurations have been discovered.With the in-depth development of research,traditional research methods have shown certain limitations.The First-principles method is an emerging research method in this field.Its precise and convenient condition control and accurate calculation results can give new vigor for DNA research.In this dissertation,we used the first-principles code package Atomic-orbital Based Ab-initio Computations at UStc(ABACUS),to study the properties of DNA and its interaction with small carcinogenic organic molecules.This dissertation is divided into six chapters.Chapter 1 introduces some basic knowledge about DNA.Chapter 2 gives a brief introduction to density functional theory.Chapter 3 introduces the functions and characteristics of this dissertation's calcu-lation tool-a first principles code package ABACUS.Chapter 4 studies the energetic and structural properties of A-form DNA under relaxed and stretching conditions.Chapter 5 goes a step further on the basis of Chapter 4,studying the energetic and structural properties of A-form DNA under greater stretching.Based on previous studies on DNA configuration changes under stretching,we tried to find DNA configu-ration changes under such conditions.It was found that the structure of DNA undergoes a structural phase change during the process of large-scale stretching,which is mani-fested as a change in repeating units and a decrease in symmetry.We propose a model to explain this phenomenon and point out that repeating units can be used as an indicator of DNA configuration classification.Chapter 6 studies the interactions between B-form DNA and a small carcinogenic organic molecule BPQ.We have discovered a new type of BPQ-DNA adducts main-tained by van der Waals interactions and compared it with the previously known co-valent BPQ-DNA adducts so that we have a more comprehensive understanding of the interactions between BPQ and DNA.