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Abstract: With the accumulation of biological knowledge and the development of computer technology, a new method of studying biology has emerged: computer simulation. Typical examples are electronic cells designed by scholars of Keio University in Japan and virtual cells designed by scholars of Connecticut State University in the United States, which allow biological experiments to run in such an artificial environment. It will be possible for biologists to use this new tool to study the mechanism of life process, which is long or complicated and difficult to complete with conventional experimental techniques. This is the inevitability of the progress of experimental biology, and it will also bring great opportunities for theoretical biology to become the pioneer of the whole life science.

Keywords: analogy, compound, cell, computer

New trends of methods in computer simulation and biological research

Zhou Jianjun, Wu Caihong, Peking University College of Life Sciences 10087 1

Fu, Institute of Zoology, Chinese Academy of Sciences 100080

Abstract: A new research method has emerged in the field of biology, which is marked by artificial laboratory and supplemented by high-quality computer and software. The most important model platform may be electronic battery or virtual battery, designed by Tomita of Keio University in Japan and Schaff and Loew of the University of Connecticut in the United States. Biologists will use this unique tool to accumulate knowledge of complex life mechanisms, which seems difficult or out of reach for traditional experimental techniques. Like physics and economics, theoretical biology will become a pioneer in the development of life science.

Keywords: simulation, complexity, cell, computer

There is such a strange phenomenon that theorists occupy the king's position in physics and economics, while in biological research, on the contrary, those who try to do theoretical research from mathematical calculation are in a neglected position. People, including researchers who actually work in the field of biology, think that biology must have been born in a laboratory full of various centrifuges, electrophoresis tanks and grotesque bottles and cans, and the writing mode of articles is almost the same, first the preface, then the materials and methods, and then the results and discussions. It is in such a living and research environment that molecular biologists collect data about birth, aging, illness and death bit by bit on the basis of direct observation and experiments, and are busy with the cloning and functional analysis of single genes all day, and the way in which single signal molecules interact with directly related protein; However, how to study life itself as a complex system as a whole has not been considered, let alone what model to use for deduction and prediction.

However, there are still some "fools" or "crazy" visionaries who continue to dream. They always want to map the life forms and wonderful processes in the real world to the computer simulation environment and create digital "artificial life". Santa Fe College (SFI) in California has such a group of "lunatics". Similar to the popular artificial intelligence, "artificial life" is to simulate the basic biological mechanism and life itself by computer, and the research scope of artificial intelligence is to simulate the human thinking process. Chris Langton began this attempt in the early 1970s. He found Feng, the originator of computers, in his reading. Neumann has been interested in self-reproduction since the 1940s, which is one of the most essential natural laws of living things, from DNA replication, cell division to bisexual reproduction. Langton turned his interest in reading into a lifelong pursuit, gathered like-minded researchers, and held the first international symposium on artificial life with SFI and Apple Computer Company in 1987, covering everything from the collective behavior of the ant kingdom, the self-organization of protein molecules to the computer evolution of ecosystems. One of the most striking is a program demonstrated by Richard Dawkins, a famous biologist at Oxford University. He once wrote The Selfish Gene, which simulates an initial simulated biological form by repeatedly using several simple rules, and depicts the process of life evolution and extinction strikingly similar to the real biological world on the computer.

People look for the physical body double in the real world from the virtual space created by computers, and complete the experimental research that is difficult to control, expensive and too dangerous for society and experimenters themselves.

Life process is a chemical process to a great extent, at least at present, it is mainly research or capable of research. After the main framework of quantum mechanics was determined in the 1920s and 1930s, the process of chemical reaction could be theoretically explained and calculated from the behavior of electrons in the outer layer of atoms. Unfortunately, there was no computer at that time. Even in the sixties and seventies, it was impossible for chemists to be interested in using programs to calculate and simulate chemical reactions between molecules. However, the situation has changed now. A software called Gaussian98 has become the darling of almost all top chemical researchers, and its excellent ability to simulate the interaction of biological macromolecules has attracted more and more researchers struggling in the biological field. Because of its great success, Watter Kohn and John A.Pople, who have made outstanding contributions to its development, invented a simpler and easier calculation method of quantum chemical density function, and turned this theoretical program into a practical tool for simulating molecular reaction process in computer environment, and won the Nobel Prize in Chemistry in 1998.

Cells are the most basic form of organisms. We can learn a lot about the complexity of life from cells, especially the classical system theory that the whole is greater than the parts. How to study the complexity of single cells, larger life forms and even tangled ecosystems is a very challenging topic for biologists. Traditional experimental research ideas and analysis methods obviously can't meet this requirement, and biologists' own skills alone are lacking. Fortunately, with the development of computer science to such a developed level today, a newly born bioinformatics straddles the two, and some elites in both computer and biology have also emerged, which is beneficial to both. Of course, this paper only expounds the influence of this megatrend on biological research.

Molecular biology, which developed in the middle of this century, has described the physical and chemical processes in cells in such detail, from gene expression to transmembrane signal transmission, from the generation and consumption of energy in cells to the unconscious birth and silent death of cells. However, no matter how clearly we know these specific processes, we still can't understand how the whole quality of life works, because what we do and observe is only one side of it, and elephants don't automatically decompose into an ear because they know they are to be touched by a group of blind people. In the past, all molecular biology experiments were done by blind people. With the acceleration and completion of the human genome project and several model biological genome projects, now we need a powerful and wonderful tool to gather these fragmented knowledge to test something and predict something. This is a computer simulation.

A research team led by Masaru Tomita, a professor of bioinformatics at Keio University in Japan, is making an epoch-making software: E-CELL. This is a biological computer simulation software, which constructs a virtual electronic cell in a computer environment. It not only includes some events and processes of individual cells, but also depicts the whole picture of cells from a holistic perspective. The beta version of the software will be released online (www.e-cell.org) in June this year. E-CELL is actually a modeling tool kit or platform, which allows users to specify cell genes, protein and other molecules, their intracellular localization and estimate their concentrations, give the "rules of the game" on which their individual interaction depends, and then leave the rest of the work to the computer to see how these "initial values" input by users interact to form cells in this complex cellular system. Electronic cells will tell you the changes of specific substances in specific positions at each moment through pictures and numbers; With the click of a mouse, you can carry out gene knockout, transgene or gene modification in the molecular biology laboratory, and freely expose the cells of interest to a certain living environment without considering bacterial pollution, RNA degradation or annoying radiation damage. All the researchers need to do is input the initial value, then have a cup of coffee in front of the computer screen and wait for the friendly E-cell simulation. Undoubtedly, this method will provide a very simple and economical means for drug screening and gene function research. More importantly, we can see the influence of a certain factor and link on the overall behavior and life activities of cells in real time. At present, this program can run under UNIX or Linux operating system. Tomita's team constructed an "imaginary cell" with 127 genes, most of which came from Ureaplasma urealyticum, which is the simplest cell and the simplest genome. This virtual cell "lives" in the computer environment, absorbs nutrients such as glucose from the virtual culture medium, synthesizes various enzymes and protein to maintain the survival of the cell, and discharges metabolic wastes such as lactic acid. Can E-CELL, which combines biology and computer science, only provide a demonstration of teaching programs that attract children like cartoons? When you can make a demonstration and its repeatability is very good, there is absolutely no human error; More importantly, it gives us a brand-new exploration environment, and we can find unknown connections from the known and test our thoughts. Tomita has an unexpected discovery: when the glucose supply of virtual cells is interrupted, the level of ATP (the most important energy supplier in all life processes) in cells actually rises briefly before falling. According to this simple simulation result, Tomita speculates that ATP itself is also needed to supply energy in the early stage of ATP production, so when the glucose source is interrupted, this self-consumption will no longer be carried out, and ATP supply will be maintained for a short time in the middle and late stages of ATP production. It can be clearly seen that the simulation experiment provides the most valuable hints and clues for the real experiment in living cells, filters out many tedious and repetitive processes, and leaves interesting topics and materials for scientists. Of course, in order to simulate properly, we must first enrich our simulation software with many materials, understand more genes and their functions, and understand the physical and chemical laws hidden in soft cells and organisms, so as to finally simulate the complete cells of "real" organisms.

Besides Tomita's efforts in E-CELL, computer scientist James Schaff and physiologist Leslie Loew of Connecticut State University Health Center are also dreaming the same dream. They designed a "virtual cell" and put it on their host (www.nrcam.uchc.edu). Users can run their own simulation experiments by logging in remotely. In addition to simulating the whole cell at the same time, cell biologists can also study how the morphological volume and other physical characteristics of cells affect the specific biochemical processes in this system. Virtual cell is an accurate measurement of molecular diffusion and how it reacts in living cells based on Loew. These results are described in mathematical language and then written into corresponding computer programs, which are "assembled" into computerized cells like real cells, which is a framework environment in which software users can avoid the constraints of specific biochemical processes. For example, researchers used mice to artificially add a certain amount of calcium to virtual cells, and then observed how virtual cells solved the fate of important signal molecules in cells and related events involving biomolecules. In addition to observing the calcium oscillation recorded in living cells, it can also predict the dynamic process of another signal molecule IP3, which is difficult to do in living cells. Researchers will get the whole process of intracellular molecular events just like watching a movie, which is an incredible relaxation and luxury compared with the hard work of experimental biologists in a messy laboratory all day.

These two kinds of simulation software can complement each other, and the information and research trends revealed in them are attracting more and more interest, especially in cell biology. Without the help of computers, they feel that life is getting harder every day. This is the most vital information science and life science, and it is a clear sign that they will blend with each other in the future 2 1. May more people believe.

At present, more and more scientific experiments, especially more complex experiments, have adopted this method and achieved very valuable conclusions, which are very worthy of reference for workers active in the field of biological development, such as the research on how long-necked dinosaurs foraged recently published in Science magazine. Long-necked sauropods lived in Jurassic and Cretaceous. When sauropod dinosaur fossils were first discovered at the beginning of this century, their necks were described as horizontal. But the recently discovered fossil was reconstructed and found that its head was far above the ground, and its swan-like curve neck was almost vertical to the ground. This immediately caused people to argue about how the blood circulation of this dinosaur provided blood for the head. Some researchers even think it may have multiple hearts. The original fossil specimen is heavy and brittle, so it is difficult to move on its joints, so it is difficult to determine the original shape of its neck. To solve this problem, Steven and parrish developed the "dinosaur form" software to simulate the neck form of two long-necked sauropods, Liang Long and Puzzled Dragon. The software simulates the geometric details of each pair of cervical vertebrae and obtains the complex 3 d images. The results show that their necks are almost horizontal when relaxed, and the downward inclination angle is very small. The head is close to the ground and has a downward angle compared with the neck. The necks of these two dinosaurs were not as soft as the traditional hypothesis thought. Liang Long could only lift his head over his back, while the confusing dragon was a little more flexible. This means that sauropods ate plants that grew on the ground near the lake, instead of eating leaves like giraffes.

With the emergence of such a research form, it is necessary for us to reflect on what is science and what is scientific method. Science, besides its extended meaning as almost synonymous with truth, is actually a social behavior under the guidance of spirit and method, which is called scientific method. Its core is the idea of repeatable control experiment, which can be used to verify various hypotheses about why the world is the world. Only a theory that has gone through such a process can be truly called a scientific theory. However, when the natural science research focuses on the most complex life system in nature, our original alcohol lamp, test tube, microscope and scalpel are not enough, and we can't even grasp the repeatability of the experiment well, because of the nonlinearity of the life system, the irreversibility of some processes and the complex and uncontrollable influence of thousands of experimental variables. We need to establish a laboratory system, a computer virtual laboratory, next to or inside the real laboratory to study the complex system of life, conduct a large-scale hypothesis-prediction-test and repeated "life game", lead the whole biological research, determine the most valuable research proposition for it, and guide it to do and what may happen. In this wonderful body body double, the dignity of science will be restored, and the interest and confidence of human beings in exploring the unknown will be restored, thus making theoretical biology ahead of experimental practice in an all-round way and supporting the foundation of conventional science in 2 1 century.

References:

1. Complexity129-184,276-336 by Mitchell Waldrop1995; Chen Ling, 1997 lived in Beijing in April? Reading? Xinzhi Sanlian Bookstore was published.

2. "Virtual and Real World-How Computer Simulation Changed the Frontier of Science", 41-kloc-0/97, written by John L. Casty in1996; Translated by Wang Qianxiang and Quan Ning, published by Shanghai Science and Technology Education Press in February 2008, 1998.

3. Dennis Nomiller. Create work unit' on computer'. Science1999,284: 80-81.

4. Kent Stevens, J Michael parrish. Neck posture and feeding habits of two Jurassic sauropods. http://China . science mag . org/CGI/content/abstract/284/54 15/798