Goals

Educational: to continue the formation of knowledge about biology as a science; give concepts about the main sections of biology and the objects they study;
Developing: to form the skills of working with literary sources, the formation of skills to make analytical connections;
Educational: broaden horizons, form a holistic perception of the world.

Tasks

1. Reveal the role of biology, among other sciences.
2. To reveal the connection of biology with other sciences.
3. Determine what different branches of biology are studying.
4. Define the role of biology in life human .
5. Draw Interesting Facts related to the topic from the videos presented in the lesson.

Terms and concepts

Biology is a complex of sciences, the objects of study of which are living beings and their interaction with the environment.
Life is an active form of the existence of matter, in a sense higher in comparison with its physical and chemical forms existence; a set of physical and chemical processes occurring in the cell, allowing metabolism and its division.
The science is a sphere of human activity aimed at the development and theoretical systematization of objective knowledge about reality.

During the classes

Knowledge update

Remember what biology studies.
Name the branches of biology you know.
Find the correct answer:
1. Botany studies:
A) plants
B) animals
B) only algae
2. The study of mushrooms takes place within the framework of:
A) botany
B) virology;
B) mycology.
3. In biology, several kingdoms are distinguished, namely:
A) 4
B) 5
AT 7
4. A person refers in biology to:
A) Animal Kingdom
B) Subclass Mammals;
C) Genus Homo sapiens.

With the help of Figure 1, remember how many kingdoms are distinguished in biology:

Rice. 1 Kingdoms of living organisms

Learning new material

For the first time the term "biology" in 1797 was proposed by the German professor T. Ruzom. But it began to be actively used only in 1802, after the use of this term J-B. Lamarck in his works.

Today, biology is a complex of sciences that form independent scientific disciplines dealing with certain objects of study.

Among the "branches" of biology, one can name such sciences as:
- botany - the science that studies plants and its subsections: mycology, lichenology, briology, geobotany, paleobotany;
- zoology- the science that studies animals, and its subsections: ichthyology, arachnology, ornithology, ethology;
- ecology - the science of the relationship of living organisms with the environment;
- anatomy - the science of internal structure all living things;
- morphology - a science that studies the external structure of living organisms;
- Cytology - the science that studies the cell;
- as well as histology, genetics, physiology, microbiology and others.

In general, you can see the totality of biological sciences in Figure 2:

Rice. 2 Biological sciences

At the same time, they allocate whole line sciences, which were formed as a result of the close interaction of biology with other sciences, and they are called integrated. These sciences can be safely attributed: biochemistry, biophysics, biogeography, biotechnology, radiobiology, space biology and others. Figure 3 shows the main integral sciences with biology

Rice. 3. Integral biological sciences

Knowledge of biology is important for a person.
Task 1: Try to formulate for yourself what exactly is the importance of biological knowledge for a person?
Activity 2: Watch the following video about evolution and determine what biological science knowledge was required to create it

And now let's remember what kind of knowledge and why a person needs:
- to determine various diseases of the body. Their treatment and prevention require knowledge about the human body, which means knowledge of: anatomy, physiology, genetics, cytology. Thanks to the achievements of biology, the industry began to produce medicines, vitamins, and biologically active substances;

In the food industry, it is necessary to know botany, biochemistry, human physiology;
- in agriculture knowledge of botany and biochemistry is necessary. Thanks to the study of the relationship between plant and animal organisms, it became possible to create biological methods for controlling pests of agricultural crops. For example, the complex knowledge of botany and zoology is manifested in agriculture, and this can be seen in a short video

And this is just a short list of the "useful role of biological knowledge" in human life.
The following video will help you better understand the role of biology in life.

It is not possible to remove the knowledge of biology from the mandatory ones, because biology studies our life, biology gives knowledge that is used in most areas of human life.

Task 3. Explain why modern biology is called a complex science.

Consolidation of knowledge

1. What is biology?
2. Name the subsections of botany.
3. What is the role of knowledge of anatomy in human life?
4. Knowledge of what sciences is necessary for medicine?
5. Who first identified the concept of biology?
6. Look at Figure 4 and determine what science is studying the depicted object:

Fig.4. What science studies this object

7. Study Figure 5, name all living organisms and the science that studies it

Rice. 5. Living organisms

Homework

1. Process the textbook material - paragraph 1
2. Write in a notebook and learn the terms: biology, life, science.
3. Write down in a notebook all sections and subsections of biology as a science, briefly characterize them.

An eyeless fish Phreaticthys andruzzii was recently discovered living in underground caves, whose internal clock is set not to 24 (as in other animals), but to 47 hours. A mutation is to blame for this, which turned off all the light-sensitive receptors on the body of these fish.

The total number of biological species living on our planet is estimated by scientists at 8.7 million, and at the moment no more than 20% of this number have been openly and classified.

Ice fish, or whitefish, live in the waters of Antarctica. This is the only vertebrate species that does not have red blood cells and hemoglobin in its blood - therefore, the blood of ice fish is colorless. Their metabolism is based only on oxygen dissolved directly in the blood.

The word "bastard" comes from the verb "fornicate" and originally meant only the illegitimate offspring of a purebred animal. Over time, in biology, this word was replaced by the term "hybrid", but it became abusive in relation to people.

List of sources used

1. Lesson "Biology - the science of life" Konstantinova E. A., teacher of biology, secondary school No. 3, Tver
2. Lesson “Introduction. Biology is the science of life” Titorov Yu.I., teacher of biology, director of the Kemerovo CL.
3. Lesson "Biology - the science of life" Nikitina O.V., teacher of biology, MOU "Secondary School No. 8, Cherepovets.
4. Zakharov V.B., Kozlova T.A., Mamontov S.G. "Biology" (4th edition) -L .: Academy, 2011.- 512s.
5. Matyash N.Yu., Shabatura N.N. Biology Grade 9 - K .: Geneza, 2009. - 253 p.

Edited and sent by Borisenko I.N.

Working on the lesson

Borisenko I.N.

Konstantinova E.A.

Titorova Yu.I.

Nikitina O.V.

Biology- the science of living nature.

Biology studies the diversity of living beings, the structure of their bodies and the work of their organs, the reproduction and development of organisms, as well as the influence of man on wildlife.

The name of this science comes from two Greek words " bios" - "life and " logos- "science, word".

One of the founders of the science of living organisms was the great ancient Greek scientist (384 - 322 BC). He was the first to generalize the biological knowledge obtained before him by mankind. The scientist proposed the first classification of animals, combining living organisms similar in structure into groups, and designated a place for a person in it.

Subsequently, many scientists who studied different types living organisms that inhabit our planet.

Bioscience family

Biology is the science of nature. The field of research of biologists is huge: these are various microorganisms, plants, fungi, animals (including humans), the structure and functioning of organisms, etc.

Thus, biology is not just a science, but whole family, consisting of many individual sciences.

Explore an interactive chart about the biological sciences family and find out what different branches of biology study.

Anatomy- the science of the form and structure of individual organs, systems and the body as a whole.

Physiology- the science of the vital activity of organisms, their systems, organs and tissues, the processes going on in the body.

Cytology- the science of the structure and activity of the cell.

Zoology is the science that studies animals.

Sections of zoology:

Entomology is the science of insects.

There are several sections in it: coleopterology (studies beetles), lepidopterology (studies butterflies), myrmecology (studies ants).

Ichthyology is the science of fish.
Ornithology is the science of birds.
Theriology is the science of mammals.

Botany the science that studies plants.

Mycology the science that studies mushrooms.

Protistology The science that studies protozoa.

Virology the science that studies viruses.

Bacteriology the science that studies bacteria.

Significance of biology

Biology is closely related to many parties practical activities human - agriculture, various industries industry, medicine.

Successful development Agriculture currently largely dependent on biologists-breeders involved in the improvement of existing and the creation of new varieties of cultivated plants and breeds of domestic animals.

Thanks to the achievements of biology, the microbiological industry has been created and is successfully developing. For example, kefir, curdled milk, yoghurts, cheeses, kvass and many other products a person receives due to the activity of certain types of fungi and bacteria. With the help of modern biotechnologies, enterprises produce medicines, vitamins, feed additives, plant protection products against pests and diseases, fertilizers and much more.

Knowledge of the laws of biology helps to treat and prevent human diseases.

Every year more and more people use Natural resources. Powerful technology is transforming the world so quickly that now there are almost no corners left on Earth with untouched nature.

To save normal conditions for human life, it is necessary to restore the destroyed natural environment. Only people can do it, okay knowing the laws nature. Knowledge of biology as well as biological science ecology helps us solve the problem of preserving and improving the conditions of life on the planet.

Complete the interactive task -

What is biology? Biology is the science of life, the living organisms that live on Earth.

Picture 3 from the presentation "Science" to biology lessons on the topic "Biology"

Dimensions: 720 x 540 pixels, format: jpg. To download a picture for free biology lesson, right-click on the image and click "Save Image As...". To show pictures in the lesson, you can also download the entire presentation "Science.ppt" with all the pictures in a zip archive for free. Archive size - 471 KB.

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Biology

"Research methods in biology" - The history of the development of biology as a science. Experiment planning, choice of methodology. Lesson plan: To solve what global problems of mankind, knowledge of biology is necessary? Topic: Boundary disciplines: Task: Morphology anatomy physiology systematics paleontology. The meaning of biology. Biology is about life.

"Scientist Lomonosov" - Emphasized the importance of exploring the Northern Sea Route, the development of Siberia. November 19, 1711 - April 15, 1765 (age 53) June 10, 1741. Discoveries. He developed atomic and molecular ideas about the structure of matter. Ideas. Excluded phlogiston from the number of chemical agents. Job. Being a supporter of deism, materialistically considered the phenomena of nature.

"Botanist Vavilov" - All-Union Institute of Applied Botany. In 1906 Vavilov Nikolai Ivanovich. In 1924, completed by: Roxana Babicheva and Lyudmila Zhdanova, students of class 10 B. Vavilov's authority as a scientist and organizer of science grew. In Merton (England), in the genetic laboratory of the Horticultural Institute. N. I. Vavilov was born on November 26, 1887 in Moscow.

"Project activity" - Alekseeva E.V. Lecture plan. The teacher becomes the author of the project. Overview of additional resources. Technologization information model educational process. Designing a biology lesson. Project activity. Theory and practice. (Project method). Stages of the teacher's work. Theory and practice. Basic blocks in projects.

"Science of wildlife" - Design of workbooks. 3. Biology - the science of wildlife. Biology is the science of living nature. bacteria. Mushrooms. They consist of one cell and do not have a nucleus. Mark Cicero. Biology studies living organisms. They have chlorophyll and form in the light organic matter releasing oxygen. Question: What does biology study?

"Mathematics in biology" - "Identification of flat feet." Reading charts. The concept of symmetry; Symmetry types. The concept of a graph of a function. General biology, Grade 10. "Construction of a variation series and a curve". The touch points will be ears. Circle, oval. It is a generally accepted point of view that mathematics belongs to the exact sciences. Proportionality.

In total there are 14 presentations in the topic

The specifics of the biological pattern for middle school students

Biological drawing is one of the universally recognized tools for studying biological objects and structures. There are many good tutorials on this issue.

For example, in the three-volume book "Biology" by Green, Stout, Taylor, the following rules for biological drawing are formulated.

1. It is necessary to use paper for drawing of the appropriate thickness and quality. Pencil lines should be well erased from it.

2. Pencils should be sharp, hardness HB (in our system - TM), not colored.

3. The drawing must be:

- large enough - the more elements make up the object under study, the larger the drawing should be;
- simple - include outlines of the structure and other important details to show the location and connection of individual elements;
- drawn with thin and distinct lines - each line must be thought out and then drawn without lifting the pencil from the paper; do not hatch or color;
- the inscriptions should be as complete as possible, the lines coming from them should not intersect; Leave space for captions around the drawing.

4. Make two drawings if necessary: a schematic drawing showing the main features, and a detailed drawing of small parts. For example, at low magnification, draw a cross-sectional plan of a plant, and at high magnification, a detailed structure of the cells (a large drawn part of the drawing is outlined on the plan with a wedge or square).

5. You should draw only what you really see, and not what you think you see, and, of course, do not copy the drawing from the book.

6. Each drawing must have a title, an indication of the magnification and projection of the sample.

Page from the book "Introduction to Zoology" (German edition late XIX century)

At first glance, it is quite simple and does not raise objections. However, we had to revise some theses. The fact is that the authors of such manuals consider the specifics of biological drawing already at the level of an institute or senior classes of special schools, their recommendations are addressed to fairly adult people with an analytical (already) mindset. In the middle (6-8th) grades - both ordinary and biological - things are not so simple.

Very often, laboratory sketches turn into mutual "torment". Ugly and little intelligible drawings are not liked by the children themselves - they just don’t know how to draw yet, nor by the teacher - because those details of the structure, because of which everything was started, are very often missed by most children. Only artistically gifted children normally cope with such tasks (and do not begin to hate them!) In short, the problem is that there are objects, but there is no adequate technique. By the way, drawing teachers sometimes face the opposite problem - there is a technique and it is difficult with the selection of objects. Maybe we should unite?

In the 57th Moscow school where I work, an integrated course of biological drawing in middle grades, within which teachers of biology and drawing work in pairs. We have developed many interesting projects. Their results have been repeatedly exhibited in Moscow museums - Zoological Moscow State University, Paleontological, Darwin, at various festivals of children's creativity. But the main thing is that ordinary children, not selected for either art or biology classes, are happy to complete these design tasks, are proud of their own work, and, as it seems to us, begin to peer into the world of the living much more closely and thoughtfully. Of course, not every school has the opportunity for biology and art teachers to work together, but some of our findings will probably be interesting and useful, even if you work only within the framework of a biology program.

Motivation: emotions first

Of course, we draw in order to better study and understand structural features, to get acquainted with the diversity of those organisms that we study in the lessons. But, no matter what task you give, remember that it is very important for children of this age to emotionally capture the beauty and expediency of the object before starting work. We try to start working on a new project with vivid impressions. Either a short video clip or a small (no more than 7-10!) selection of slides is best suited for this. Our comments are directed at the unusualness, beauty, amazingness of objects, even if it is something ordinary: for example, the winter silhouettes of trees when studying the branching of shoots - they can either be frosty and reminiscent of corals, or emphasized graphic - black on white snow. Such an introduction should not be long - just a few minutes, but it is very important for motivation.

Progress: Analytical Build

Then you move on to the formulation of the task. Here it is important to first highlight those features of the structure that determine the appearance of the object, and show their biological meaning. Of course, all this must be written on the board and written in a notebook. Actually, right now you are setting a working task for the students - to see and display.

And then, on the second half of the board, you describe the stages of building a drawing, supplementing them with diagrams, i.e. describe the methodology and procedure. In essence, you yourself quickly complete the task in front of the children, keeping on the board the whole series of auxiliary and intermediate constructions.

At this stage, it is very good to show the children finished drawings, either by artists who depicted the same objects, or by successful work of previous students. It must be constantly emphasized that a good and beautiful biological drawing is essentially a study - i.e. the answer to the question of how the object works, and over time, teach children to formulate these questions themselves.

Proportions, auxiliary lines, detailing, leading questions

Building a drawing - and exploring the object! - you start by finding out its proportions: the ratio of length to width, parts to the whole, be sure to set a fairly rigid format for the picture. It is the format that will automatically determine the degree of detail: big number details, a large one will require saturation with details and, therefore, more time to work. Think in advance what is more important to you in each case.

1) draw an axis of symmetry;

2) build two pairs of symmetrical rectangles - for the upper and lower wings (for example, dragonflies), first determining their proportions;

3) fit into these rectangles the curved lines of the wings

Rice. 1. 7th grade. Theme "Squads of insects." Ink, pen on pencil, from satin

(I remember a funny, sad and ordinary story that happened when I first did this work. A seventh grade boy first understood the word “fit in” as easy to fit inside and drew curved circles inside the rectangles - all four are different! Then, after my prompting, what to enter - means touching the auxiliary lines, he brought a butterfly with rectangular wings, only slightly smoothed at the corners. And only then I guessed to explain to him that the inscribed curve touches each side of the rectangle at only one point. And we had to redo the drawing again ...)

4) ... This point can be located in the middle of the side or at a distance of one third from the corner, and this must also be determined!

But how happy he was when his drawing got to the school exhibition - for the first time - it worked! And now I pronounce all the stages of our torment with him in the description of the “Progress of work”.

Further detailing of the drawing just leads us to a discussion of the biological meaning of many features of the object. Continuing the example with insect wings (Fig. 2), we discuss what veins are, how they are arranged, why they necessarily merge into a single network, how the nature of venation differs in insects of different systematic groups (for example, in ancient and new-winged), why the extreme the vein of the forewings is thickened, etc. And try to give most of your instructions in the form of questions that children need to find answers to.

Rice. 2. "Dragonfly and antlion." 7th grade, topic "Squads of insects." Ink, pen on pencil, from satin

By the way, try to pick up more objects of the same type, giving the guys a choice. At the end of the work, the class will see both the biological diversity of the group, and important common features of the structure, and, finally, the different drawing abilities of children will not be so important.

Unfortunately, the school teacher does not always have a sufficient number of various objects of the same group at his disposal. Perhaps our experience will be useful to you: when studying a group, we first make a frontal drawing of an easily accessible object from life, and then individually - drawings of various objects from photographs or even from drawings by professional artists.

Rice. 3. Shrimp. 7th grade, theme "Crustaceans". Pencil, from nature

For example, in the topic “Crustaceans” in the laboratory work “External structure of a crustacean”, we all first draw shrimp (instead of crayfish) bought frozen in a grocery store (Fig. 3), and then, after watching a short video clip, individually - different planktonic crustacean larvae (Fig. 4), depicted in "The Life of Animals": on large (A3) sheets, tinted with watercolor in coldish gray, blue, greenish tones; chalk or white gouache, working through fine details with ink and pen. (Explaining how to convey the transparency of planktonic crustaceans, we can offer the simplest model - a glass jar with an object enclosed in it.)

Rice. 4. Plankton. 7th grade, theme "Crustaceans". Toned paper (A3 format), chalk or white gouache, black ink, from satin

In the 8th grade, when studying fish, in the laboratory work “External structure of bone fish”, we first draw an ordinary roach, and then the guys draw representatives of different fish orders with watercolors from the magnificent color tables “Commercial fish” that we have at school.

Rice. 5. Skeleton of a frog. 8th grade, theme "Amphibians". Pencil, with educational preparation

When studying amphibians first - laboratory work"Structure of the skeleton of a frog", drawing in a simple pencil (Fig. 5). Then, after watching a short video clip, a watercolor drawing of various exotic leaf-climbing frogs, etc. (We draw from calendars with high-quality photographs, fortunately, they are not uncommon now.)

With such a scheme, rather boring pencil drawings of the same object are perceived as a normal preparatory stage for bright and individual works.

Important: technique

The choice of technique is very important for the successful completion of the work. In the classic version, you should take a simple pencil and white paper, but .... Our experience says that from the point of view of children, such a drawing will look unfinished, they will remain dissatisfied with the work.

Meanwhile, it is enough to make a pencil sketch in ink, and even take tinted paper (we often use colored paper for printers) - and the result will be perceived quite differently (Fig. 6, 7). The feeling of incompleteness is often created precisely by the lack of a detailed background, and the easiest way to solve this problem is with the help of tinted paper. In addition, using ordinary chalk or a white pencil, you can almost instantly achieve a glare or transparency effect, which is often necessary.

Rice. 6. Radiolaria. 7th grade, the topic "The simplest". Tinted paper (A3 format) for watercolor (with a rough texture), ink, pastel or chalk, from satin

Rice. 7. Bee. 7th grade, topic "Squads of insects." Ink, pen on pencil, volume - with a brush and diluted ink, small details with a pen, from a satin

If it is difficult for you to organize work with mascara, use soft black liners or rollerballs (at worst, gel pens) - they give the same effect (Fig. 8, 9). Using this technique, be sure to show how much information is given by using lines of different thicknesses and pressure - both to highlight the most important thing and to create the effect of volume (foreground and background). You can also use moderate and light shading.

Rice. 8. Oats. 6th grade, topic "Variety of flowering plants, family Cereals." Ink, tinted paper, from the herbarium

Rice. 9. Horsetail and club moss. 6th grade, topic "Spore plants". Ink, white paper, from the herbarium

In addition, unlike classical scientific drawings, we often do the work in color or use light toning to show volume (Fig. 10).

Rice. 10. Elbow joint. 9th grade, topic "Musculoskeletal system". Pencil, with plaster aid

Of the color techniques, we tried many - watercolor, gouache, pastel, and eventually settled on soft colored pencils, but always on rough paper. If you decide to try this technique, there are a few important things to keep in mind.

1. Pick up soft quality pencils from a good company, such as Kohinoor, but do not give children a large range of colors (basic enough): in this case, they usually try to pick up a ready-made color, which of course fails. Show how to get the right shade by mixing 2-3 colors. To do this, you need to work with a palette - a piece of paper on which they select the desired combinations and pressure.

2. Rough paper will greatly facilitate the task of using weak and strong colors.

3. Light short strokes should, as it were, sculpt the shape of the object: i.e. repeat the main lines (and not paint, contrary to the shape and contours).

4. Then you need the final juicy and strong strokes, when the right colors have already been selected. It is often worth adding highlights, which will greatly enliven the drawing. The easiest way is to use ordinary chalk for this (on tinted paper) or go through with a soft eraser (on white). By the way, if you use loose techniques - chalk or pastel - you can then fix the work with hairspray.

When mastering this technique, you will be able to use it in nature, with a lack of time, literally “on your knee” (just don’t forget about tablets - just a piece of packing cardboard is enough!).

And, of course, for the success of our work, we definitely arrange exhibitions - sometimes in the classroom, sometimes in the corridors of the school. Quite often, children's reports on the same topic are timed to the exhibition - both oral and written. In general, such a project leaves you and the children with a feeling of great and beautiful work, which is worth preparing for. Probably, with contact and mutual interest with a drawing teacher, you can start working in biology lessons: analytical preparatory stage studying the object, creating a pencil sketch, and finishing it in the technique you have chosen together - in his lessons.

Here is an example. Botany, topic "Escape - bud, branching, structure of the shoot." A branch with buds - large in the foreground, in the background - the silhouettes of trees or shrubs against the background of white snow and black sky. Technique - black ink, white paper. Branches - from nature, silhouettes of trees - from photographs or book drawings. The name is "Trees in Winter", or "Winter Landscape".

Another example. When studying the topic “Squads of insects”, we perform a short work “The shape and volume of beetles”. Any technique that conveys chiaroscuro and highlights (watercolor, ink with water, brush), but monochrome, so as not to be distracted from the consideration and image of the form (Fig. 11). It is better to work out the details with a pen or a gel pen (if you use a magnifying glass, the paws and head will turn out better).

Rice. 11. Beetles. Ink, pen on pencil, volume - with a brush and diluted ink, small details with a pen, from a satin

1-2 beautiful works in a quarter are enough - and drawing a living thing will delight all participants in this difficult process.

The life sciences are moving from big to small. More recently, biology described only the external features of animals, plants, bacteria. Molecular biology studies living organisms at the level of interactions between individual molecules. Structural biology - studies processes in cells at the level of atoms. If you want to learn how to “see” individual atoms, how structural biology works and “lives”, and what instruments it uses, you are here!

The general partner of the cycle is the company: the largest supplier of equipment, reagents and consumables for biological research and production.

One of the main missions of "Biomolecule" is to get to the very roots. We do not just tell what new facts the researchers discovered - we talk about how they discovered them, we try to explain the principles of biological methods. How do you take a gene out of one organism and insert it into another? How to follow the fate of a few tiny molecules in a huge cell? How to excite one tiny group of neurons in a huge brain?

And so we decided to talk about laboratory methods more systematically, to bring together in one rubric the most important, most modern biological methods. To make it more interesting and clearer, we have illustrated the articles thickly and even added animations here and there. We want the articles of the new rubric to be interesting and understandable even to a casual passer-by. And on the other hand, they should be so detailed that even a professional could find something new in them. We have collected methods into 12 large groups and are going to make a biomethodological calendar based on them. Wait for updates!

Why Structural Biology?

As you know, biology is the science of life. She appeared in early XIX centuries and the first hundred years of its existence was purely descriptive. The main task of biology at that time was considered to find and characterize as possible large quantity species of various living organisms, a little later - to identify family ties between them. Over time and with the development of other areas of science, several branches with the prefix "molecular" emerged from biology: molecular genetics, molecular biology and biochemistry - sciences that study living things at the level of individual molecules, and not according to appearance organism or the relative position of its internal organs. Finally, quite recently (in the 50s of the last century), such a field of knowledge appeared as structural biology- a science that studies processes in living organisms at the level of change spatial structure individual macromolecules. In fact, structural biology is at the intersection of three different sciences. Firstly, this is biology, because science studies living objects, and secondly, physics, since the widest arsenal of physical experimental methods, and thirdly, chemistry, since changing the structure of molecules is the object of this particular discipline.

Structural biology studies two main classes of compounds - proteins (the main "working body" of all known organisms) and nucleic acids(the main "information" molecules). It is thanks to structural biology that we know that DNA has a double helix structure, that tRNA should be depicted as a vintage letter "G", and that the ribosome has a large and small subunit, consisting of proteins and RNA in a certain conformation.

global goal structural biology, like any other science, is to "understand how things work." In what form is the protein chain folded, which causes cells to divide, how does the packaging of the enzyme change during chemical process, which it carries out, in what places the growth hormone and its receptor interact - these are the questions that this science answers. Moreover, a separate goal is to accumulate such a volume of data that these questions (for an object that has not yet been studied) can be answered on a computer without resorting to an expensive experiment.

For example, you need to understand how the bioluminescence system works in worms or fungi - they deciphered the genome, based on these data they found the desired protein and predicted its spatial structure along with the mechanism of work. True, it is worth recognizing that so far such methods exist only in their infancy, and it is still impossible to accurately predict the structure of a protein, having only its gene. On the other hand, the results of structural biology have applications in medicine. As many researchers hope, knowledge about the structure of biomolecules and about the mechanisms of their work will allow the development of new drugs on a rational basis, and not by trial and error (high-throughput screening, strictly speaking), as is most often done now. And it's not Science fiction: There are already many drugs created or optimized using structural biology.

History of structural biology

The history of structural biology (Fig. 1) is quite short and starts in the early 1950s, when James Watson and Francis Crick, based on data from Rosalind Franklin on X-ray diffraction on DNA crystals, assembled a model of the now known double helix from a vintage designer. A little earlier, Linus Pauling built the first plausible model of the helix, one of the basic elements of the secondary structure of proteins (Fig. 2).

Five years later, in 1958, the world's first protein structure was determined - myoglobin (protein of muscle fibers) of the sperm whale (Fig. 3). Of course, it did not look as beautiful as modern structures, but it was a significant milestone in the development of modern science.

Figure 3b. The first spatial structure of a protein molecule. John Kendrew and Max Perutz demonstrate the spatial structure of myoglobin assembled from a special constructor.

Ten years later, in 1984–1985, the first structures were identified by nuclear magnetic resonance spectroscopy. Since that moment, several key discoveries have taken place: in 1985 they obtained the structure of the first complex of the enzyme with its inhibitor, in 1994 they determined the structure of ATP synthase, the main “machine” of the power plants of our cells (mitochondria), and already in 2000 they received the first spatial structure "factories" of proteins - ribosomes, consisting of proteins and RNA (Fig. 6). In the 21st century, the development of structural biology has gone by leaps and bounds, accompanied by an explosive growth in the number of spatial structures. The structures of many classes of proteins have been obtained: hormone and cytokine receptors, G-protein coupled receptors, toll-like receptors, proteins immune system and many others.

With the advent of new technologies for recording and processing images of cryoelectron microscopy in the 2010s, many complex structures of membrane proteins appeared in ultra-high resolution,. The progress of structural biology did not go unnoticed: 14 Nobel Prizes, of which five are already in the 21st century.

Structural biology methods

Research in the field of structural biology is carried out with the help of several physical methods, of which only three make it possible to obtain spatial structures of biomolecules in atomic resolution. Structural biology methods are based on measuring the interaction of the test substance with various types electromagnetic waves or elementary particles. All techniques require significant financial resources - the cost of equipment is often amazing.

Historically, the first method of structural biology is X-ray diffraction analysis (XRD) (Fig. 7). As early as the beginning of the 20th century, it was found out that according to the X-ray diffraction pattern on crystals, one can study their properties - the type of cell symmetry, the length of bonds between atoms, etc. If, however, there are organic compounds, then it is possible to calculate the coordinates of the atoms, and, consequently, the chemical and spatial structure of these molecules. This is how the structure of penicillin was obtained in 1949, and in 1953 the structure of the DNA double helix.

It would seem that everything is simple, but there are nuances.

First, it is necessary to somehow obtain crystals, and their size must be sufficiently large (Fig. 8). If for not very complex molecules this is doable (remember how crystallize salt or blue vitriol!), then the crystallization of proteins is the most difficult task, which requires a non-obvious procedure for finding optimal conditions. Now this is done with the help of special robots that prepare and monitor hundreds of different solutions in search of “sprouted” protein crystals,. However, in the early days of crystallography, obtaining a protein crystal could take years of valuable time.

Secondly, on the basis of the obtained data (“raw” diffraction patterns; Fig. 8), it is necessary to “calculate” the structure. Now this is also a routine task, but 60 years ago, in the era of lamp technology and punched cards, it was far from being so simple.

Thirdly, even if it was possible to grow a crystal, it is not at all necessary that the spatial structure of the protein will be determined: for this, the protein must have the same structure at all lattice sites, which is far from always the case.

And fourthly, the crystal is far from the natural state of the protein. Studying proteins in crystals is like studying people by stuffing ten of them into a small, smoky kitchen: you can find out that people have arms, legs, and a head, but the behavior may not be quite the same as in a comfortable environment. However, X-ray diffraction analysis is the most common method for determining spatial structures, and 90% of the content of the PDB is obtained using this method.

SAR requires powerful sources of X-rays - electron accelerators or free electron lasers (Fig. 9). Such sources are expensive - several billion US dollars - but typically one source is used by hundreds or even thousands of groups around the world for a fairly nominal fee. There are no powerful sources in our country, so most scientists travel from Russia to the USA or Europe to analyze the obtained crystals. You can read more about these romantic studies in the article " Laboratory for Advanced Research on Membrane Proteins: From Gene to Angstrom» .

As already mentioned, X-ray diffraction analysis requires a powerful source of X-rays. The more powerful the source, the smaller the size of the crystals you can get by with, and the less pain biologists and genetic engineers will have to endure trying to get the unfortunate crystals. X-ray radiation is easiest to obtain by accelerating an electron beam in synchrotrons or cyclotrons - giant ring accelerators. When an electron experiences acceleration, it emits electromagnetic waves in the desired frequency range. Recently, new super-powerful radiation sources have appeared - free electron lasers (XFEL).

The principle of operation of the laser is quite simple (Fig. 9). First, the electrons are accelerated to high energy using superconducting magnets (the length of the accelerator is 1–2 km), and then they pass through the so-called undulators - sets of magnets of different polarity.

Figure 9. The principle of operation of a free electron laser. The electron beam is accelerated, passes through the undulator and emits gamma rays that fall on biological samples.

Passing through the undulator, the electrons begin to periodically deviate from the direction of the beam, experiencing acceleration and emitting x-rays. Since all electrons move in the same way, the radiation is amplified due to the fact that other electrons in the beam begin to absorb and re-emit X-ray waves of the same frequency. All electrons emit radiation synchronously in the form of a super-powerful and very short flash (with a duration of less than 100 femtoseconds). The power of the X-ray beam is so high that one short flash turns a small crystal into plasma (Fig. 10), however, in those few femtoseconds, while the crystal is intact, an image can be obtained highest quality due to the high intensity and coherence of the beam. The cost of such a laser is 1.5 billion dollars, and there are only four such installations in the world (located in the USA (Fig. 11), Japan, Korea and Switzerland). In 2017, it is planned to put into operation the fifth - European - laser, in the construction of which Russia also participated.

Figure 10. Transformation of proteins into plasma in 50 fs under the action of a free electron laser pulse. Femtosecond = 1/1000000000000000 of a second.

About 10% of the spatial structures in the PDB database were determined using NMR spectroscopy. There are several heavy-duty sensitive NMR spectrometers in Russia, which are used for world-class work. The largest NMR laboratory not only in Russia, but throughout the entire area east of Prague and west of Seoul, is located at the Institute of Bioorganic Chemistry, Russian Academy of Sciences (Moscow).

The NMR spectrometer is a wonderful example of the triumph of technology over reason. As we have already mentioned, a powerful magnetic field is required to use the NMR spectroscopy method, so the heart of the device is a superconducting magnet - a special alloy coil immersed in liquid helium (−269 ° C). Liquid helium is needed to achieve superconductivity. To prevent helium from evaporating, a huge tank with liquid nitrogen (−196 °C) is built around it. Although it is an electromagnet, it does not consume electricity: a superconducting coil has no resistance. However, the magnet must be constantly "fed" with liquid helium and liquid nitrogen (Fig. 15). If you don’t follow it, then a “quench” will occur: the coil will heat up, the helium will evaporate explosively, and the device will break ( cm. video). It is also important that the field in a sample 5 cm long be extremely uniform, so the device contains a couple of dozen small magnets needed to fine-tune the magnetic field.

Video. The planned "quench" of the 21.14-tesla NMR spectrometer.

To carry out measurements, you need a sensor - a special coil that both generates electromagnetic radiation and registers a "reverse" signal - the oscillation of the magnetic moment of the sample. To improve sensitivity by a factor of 2-4, the sensor is cooled to -200 °C, thereby getting rid of thermal noise. To do this, they build a special machine - a cryoplatform, which cools helium to the desired temperature and pumps it near the detector.

There is a whole group of methods based on the phenomenon of light scattering, x-rays or neutron beams. Based on the intensity of radiation/particle scattering at various angles, these methods make it possible to determine the size and shape of molecules in solution (Fig. 16). Scattering cannot determine the structure of a molecule, but it can be used as an aid when using another method, such as NMR spectroscopy. Instruments for measuring light scattering are relatively cheap, costing "only" about $100,000, while other methods require a particle accelerator on hand that can create a beam of neutrons or a powerful beam of X-rays.

Another method by which the structure cannot be determined, but some important data can be obtained, is resonant fluorescence energy transfer(FRET) . The method uses the phenomenon of fluorescence - the ability of some substances to absorb light of one wavelength, emitting light of a different wavelength. It is possible to choose a pair of compounds, in one of which (donor) the light emitted during fluorescence will correspond to the characteristic absorption wavelength of the second (acceptor). Irradiate the donor with a laser of the desired wavelength and measure the fluorescence of the acceptor. The FRET effect depends on the distance between the molecules, so if you introduce a fluorescence donor and acceptor into the molecules of two proteins or different domains (structural units) of one protein, you can study the interactions between proteins or the mutual arrangement of domains in a protein. Registration is carried out using an optical microscope; therefore, FRET is a cheap, albeit uninformative, method, the use of which is associated with difficulties in data interpretation.

Finally, it is impossible not to mention the "dream method" of structural biologists - computer modeling (Fig. 17). The idea of the method is to use modern knowledge about the structure and behavior of molecules to model the behavior of a protein in a computer model. For example, using the method molecular dynamics, it is possible to track the movements of a molecule or the process of protein “assembly” (folding) in real time for one “but”: the maximum time that can be calculated does not exceed 1 ms, which is extremely short, but, moreover, requires enormous computing resources (Fig. 18) . It is possible to study the behavior of the system for a longer time, only this is achieved at the cost of an unacceptable loss of accuracy.

Computer modeling is actively used to analyze the spatial structures of proteins. Docking is used to look for potential drugs that have a high propensity to interact with the target protein. At the moment, the accuracy of predictions is still low, but docking can significantly narrow the range of potential active substances that need to be tested for the development of a new drug.

Main field practical application results of structural biology is the development of drugs or, as it is now fashionable to say, drug design. There are two ways to develop a drug based on structural data: you can start from a ligand or from a target protein. If several drugs acting on the target protein are already known, and the structures of the protein-drug complexes have been obtained, it is possible to create a model of the "ideal drug" in accordance with the properties of the "pocket" of binding on the surface of the protein molecule, highlight the necessary features of the potential drug and search among all known natural and not so compounds. You can even build relationships between the properties of the structure of the drug and its activity. For example, if a molecule has a bow on top, then its activity is higher than that of a molecule without a bow. And the more the bow is charged, the better the medicine works. So, of all known molecules, you need to find a compound with the largest charged bow.

Another way is to use the target structure on the computer to search for compounds that are potentially capable of interacting with it in the right place. In this case, a library of fragments is usually used - small pieces of substances. If you find several good fragments that interact with the target in different places, but close to each other, you can build a drug from the fragments by “sewing” them together. There are many examples of successful drug development using structural biology. The first successful case dates back to 1995 when dorzolamide, a glaucoma drug, was approved for use.

The general trend in biological research is increasingly leaning towards not only a qualitative but also a quantitative description of nature. Structural biology is a prime example of this. And there is every reason to believe that it will continue to benefit not only fundamental science, but also medicine and biotechnology.

Calendar

Based on the articles of the special project, we decided to make a calendar "12 methods of biology" for 2019. This article represents March.

Literature

Bioluminescence: A Resurgence;
The triumph of computer methods: the prediction of the structure of proteins;
Heping Zheng, Katarzyna B Handing, Matthew D Zimmerman, Ivan G Shabalin, Steven C Almo, Wladek Minor. (2015).