Specifics of biological drawing for middle school students

Biological drawing is one of the generally accepted tools for studying biological objects and structures. There are many good techniques that address this problem.

For example, in the three-volume book “Biology” by Green, Stout, and Taylor, the following rules of biological drawing are formulated.

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

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

3. The drawing should be:

– large enough – the more elements that 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 relationship 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 paint;
– the inscriptions should be as complete as possible, the lines coming from them should not intersect; Leave space around the drawing for signatures.

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

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

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

A page from the book "Introduction to Zoology" (German edition of the late 19th century)

At first glance, it is quite simple and does not raise any objections. However, we had to reconsider 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 (already) analytical mindset. In the middle (6th–8th) grades – both regular and biological – things are not so simple.

Very often, laboratory sketches turn into mutual “torment.” Ugly and incomprehensible drawings are not liked either by the children themselves - they simply do not know how to draw yet - or 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 cope well with such tasks (and do not begin to hate them!). In short, the problem is that there are facilities, but there is no adequate technology. By the way, art teachers sometimes face the opposite problem - they have the technique and it is difficult to select objects. Maybe we should unite?

In the 57th Moscow school where I work, an integrated course of biological drawing in middle grades has existed for quite a long time and continues to develop, in which biology and drawing teachers work in pairs. We have developed many interesting projects. Their results were repeatedly exhibited in Moscow museums - Zoological Moscow State University, Paleontological, Darwin, and at various festivals of children's creativity. But the main thing is that ordinary children, not selected for either art or biology classes, carry out these project tasks with pleasure, are proud of their own works and, as it seems to us, begin to peer into the living world 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 biology program.

Motivation: emotions come first

Of course, we draw in order to better study and understand the structural features, to get acquainted with the diversity of the organisms that we study in class. But, no matter what task you give, remember that it is very important for children of this age to be emotionally captivated by the beauty and purposefulness of the object before starting work. We try to start work on a new project with bright impressions. The best way to do this is either a short video fragment or a small (no more than 7-10!) selection of slides. Our comments are aimed at the unusualness, beauty, amazingness of objects, even if it is something ordinary: for example, winter silhouettes of trees when studying the branching of shoots - they can be either frosty and reminiscent of corals, or emphatically graphic - black on white snow. This introduction does not have to be long - just a few minutes, but it is very important for motivation.

Work progress: analytical construction

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

And then, on the second half of the board, you describe the stages of constructing the drawing, supplementing them with diagrams, i.e. outline the methodology and order of work. Essentially, you yourself quickly complete the task in front of the children, keeping the entire series of auxiliary and intermediate constructions on the board.

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

Proportions, auxiliary lines, detailing, leading questions

Constructing a drawing - and studying the object! – you start by figuring out its proportions: the ratio of length to width, parts to the whole, being sure to set the format of the drawing quite rigidly. It is the format that will automatically determine the level of detail: a small one will lose a large number of details, a large one will require saturation with details and, therefore, more time to work. Think in advance about what is more important to you in each specific case.

1) draw the axis of symmetry;

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

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

Rice. 1. 7th grade. Theme: “Orders of insects.” Ink, pen on pencil, from satin

(I remember a funny, sad and ordinary story that happened when I first carried out this work. A seventh-grader boy first understood the word “fit” as simply fit inside and drew crooked circles inside the rectangles - all four different! Then, after my hint, what to fit - means touching the auxiliary lines, he brought a butterfly with rectangular wings, only slightly smoothed at the corners. And only then did I realize to explain to him that the inscribed curve touches each side of the rectangle only at 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 also needs to be determined!

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

Further detailing of the drawing leads us to a discussion of the biological meaning of many of the features of the object. Continuing the example with insect wings (Fig. 2), we discuss what veins are, how they are structured, 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 insects), why the extreme the vein of the fore wings is thickened, etc. And try to give most of your instructions in the form of questions to which children need to find answers.

Rice. 2. “Dragonfly and Antlion.” 7th grade, topic “Orders of insects.” Ink, pen on pencil, from satin

By the way, try to select more objects of the same type, giving the children the opportunity to choose. At the end of the work, the class will see the biological diversity of the group, and important common structural features, and, finally, the different drawing abilities of children will not be so important.

Unfortunately, the school teacher does not always have at his disposal a sufficient number of diverse objects of one group. You may find our experience useful: 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, topic “Crustaceans”. Pencil, from life

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 at a grocery store (Fig. 3), and then, after watching a short video clip, individually - different planktonic crustacean larvae (Fig. 4), depicted in “Life of Animals”: ​​on large (A3) sheets, tinted with watercolors in cool gray, blue, greenish tones; chalk or white gouache, working out fine details with ink and pen. (When explaining how to convey the transparency of planktonic crustaceans, we can offer the simplest model - a glass jar with an object placed in it.)

Rice. 4. Plankton. 7th grade, topic “Crustaceans”. Tinted paper (A3 format), chalk or white gouache, black ink, from satin

In the 8th grade, when studying fish, during the laboratory work “External structure of bony fish,” we first draw an ordinary roach, and then the children use watercolors to draw representatives of different orders of fish from the magnificent color tables “Commercial Fishes” that we have at school.

Rice. 5. Skeleton of a frog. 8th grade, topic “Amphibians”. Pencil, with educational preparation

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

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

Equally important: technology

The choice of technology is very important for the successful completion of the job. In the classic version, you would need to take a simple pencil and white paper, but... . Our experience says that from the children's point of view such a drawing will look unfinished and 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 completely differently (Fig. 6, 7). The feeling of incompleteness is often created 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 regular chalk or a white pencil, you can almost instantly achieve the effect of glare or transparency, which is often needed.

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

Rice. 7. Bee. 7th grade, topic “Orders of insects.” Ink, pen on pencil, volume - with a brush and diluted ink, fine details with pen, from satin

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

Rice. 8. Oats. 6th grade, topic “Diversity of flowering plants, family Cereals.” Ink, tinted paper, from herbarium

Rice. 9. Horsetail and moss. 6th grade, topic “Spore-bearing plants.” Ink, white paper, from herbarium

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

Rice. 10. Elbow joint. 9th grade, topic “Musculoskeletal system.” Pencil, from plaster aid

We tried many color techniques - watercolor, gouache, pastel and ultimately 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. Choose soft, high-quality pencils from a good company, such as Kohinoor, but do not give children a wide range of colors (basic enough): in this case, they usually try to choose a ready-made color, which of course fails. Show how to achieve the right shade by mixing 2-3 colors. To do this, they need to work with a palette - a piece of paper on which they select the desired combinations and pressure.

2. Rough paper will make the task of using weak and strong colors much easier.

3. Light short strokes should, as it were, sculpt the shape of the object: i.e. repeat the main lines (rather than color, contradicting the shape and contours).

4. Then you need the finishing touches, rich and strong, when the right colors have already been selected. It is often worth adding highlights, which will greatly enliven the drawing. The simplest thing is to use regular chalk (on tinted paper) or use a soft eraser (on white paper). By the way, if you use loose techniques - chalk or pastel - you can then fix the work with hairspray.

Once you master this technique, you will be able to use it in nature, if you don’t have enough time, literally “on your knees” (just don’t forget about tablets - a piece of packaging cardboard is enough!).

And, of course, for the success of our work, we definitely organize exhibitions - sometimes in the classroom, sometimes in the school corridors. Quite often, children's reports on the same topic are timed to coincide with the exhibition - both oral and written. Overall, such a project leaves you and the children with the feeling of a big and beautiful job worth preparing for. Probably, with contact and mutual interest with an art teacher, you can begin work in biology lessons: the analytical preparatory stage of studying an object, creating a pencil sketch, and finish it in the technique you have chosen together - in his lessons.

Here's an example. Botany, topic “Escape - bud, branching, shoot structure.” A branch with buds is large in the foreground, in the background there are silhouettes of trees or bushes against a background of white snow and a black sky. Technique: black ink, white paper. Branches - from life, silhouettes of trees - from photographs or book drawings. The title is “Trees in Winter”, or “Winter Landscape”.

Another example. When studying the topic “Orders of Insects”, we do a short work on “Shape and volume of beetles”. Any technique that conveys light and shade and highlights (watercolor, ink with water, brush), but monochrome, so as not to be distracted from examining and depicting the form (Fig. 11). It is better to work out the details with a pen or gel pen (if you use a magnifying glass, the legs and head will turn out better).

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

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

Biology- science of living nature.

Biology studies the diversity of living beings, the structure of their bodies and the functioning of their organs, the reproduction and development of organisms, as well as the influence of humans on living nature.

The name of this science comes from two Greek words “ bios" - "life" and " logo"-"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 acquired by humanity before him. The scientist proposed the first classification of animals, combining living organisms similar in structure into groups, and designated a place for humans in it.

Subsequently, many scientists who studied different types of living organisms inhabiting our planet made contributions to the development of biology.

Life Sciences Family

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

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

Explore the interactive diagram about the biological sciences family and find out what the 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 functions of organisms, their systems, organs and tissues, and the processes occurring in the body.

Cytology- the science of the structure and functioning of cells.

Zoology - the science that studies animals.

Sections of Zoology:

• Entomology is the science of insects.

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

The meaning of biology

Biology is closely related to many aspects of human practical activity - agriculture, various industries, medicine.

The successful development of agriculture today largely depends on biologists-breeders involved in improving existing and creating new varieties of cultivated plants and breeds of domestic animals.

Thanks to the achievements of biology, the microbiological industry was created and is successfully developing. For example, people obtain kefir, yogurt, yoghurt, cheese, kvass and many other products thanks to the activity of certain types of fungi and bacteria. Using modern biotechnologies, enterprises produce medicines, vitamins, feed additives, plant protection products from pests and diseases, fertilizers and much more.

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

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

In order to maintain normal conditions for human life, it is necessary to restore the destroyed natural environment. This can only be done by people who know the laws of nature well. Knowledge of biology as well as biological science ecology helps us solve the problem of preserving and improving living conditions on the planet.

Complete the interactive task -

Goals

• Educational: continue to develop knowledge about biology as a science; give concepts about the main branches of biology and the objects they study;
• Developmental: to develop skills in working with literary sources, developing the ability to make analytical connections;
• Educational: broaden your horizons, form a holistic perception of the world.

Tasks

1. Reveal the role of biology, among other sciences.
2. Reveal the connection between biology and other sciences.
3. Determine what different branches of biology study.
4. Determine the role of biology in life person .
5. Learn interesting facts about the topic from the videos presented in the lesson.

Terms and concepts

• Biology is a complex of sciences whose objects of study are living beings and their interaction with the environment.
• Life is an active form of existence of matter, in a sense higher than its physical and chemical forms of existence; a set of physical and chemical processes occurring in a cell that allow metabolism and cell division.
• Science is a sphere of human activity aimed at developing and theoretically systematizing objective knowledge about reality.

Lesson progress

Updating knowledge

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

Using Figure 1, remember how many kingdoms are distinguished in biology:

Rice. 1 Kingdoms of living organisms

Learning new material

The term “biology” was first proposed in 1797 by the German professor T. Rusom. But it began to be actively used only in 1802, after the use of this term reinforced concrete. Lamarck in his works.

Today, biology is a complex of sciences that is formed by independent scientific disciplines that deal with specific objects of research.

Among the “branches” of biology, we can name such sciences as:
- botany is a science that studies plants and its subsections: mycology, lichenology, bryology, geobotany, paleobotany;
- zoology– the science that studies animals and its subsections: ichthyology, arachnology, ornithology, ethology;
- ecology is the science of the relationship between living organisms and the external environment;
- anatomy - the science of the internal structure of all living things;
- morphology is a science that studies the external structure of living organisms;
- cytology is a science that deals with the study of cells;
- 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, a whole series of sciences are distinguished, which were formed as a result of the close interaction of biology with other sciences, and they are called integrated. Such sciences can safely include: biochemistry, biophysics, biogeography, biotechnology, radiobiology, space biology and others. Figure 3 shows the main sciences integral to biology

Rice. 3. Integral biological sciences

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

Now let’s remember what kind of knowledge a person needs and why:
- 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, 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 required. Thanks to the study of the relationships between plant and animal organisms, it has become possible to create biological methods for controlling crop pests. 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 understand more about the role of biology in life.

It is not possible to remove knowledge of biology from mandatory knowledge, because biology studies our life, biology provides knowledge that is used in most spheres 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 the sections and subsections of biology as a science, briefly characterize them.

Recently, an eyeless fish, Phreatichthys andruzzii, was discovered living in underground caves, whose internal clock is set not to 24 (like other animals), but to 47 hours. A mutation is to blame for this, which turned off all 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 no more than 20% of this number has been discovered and classified at the moment.

Ice fish, or whitefish, live in Antarctic waters. This is the only species of vertebrate in which there are no red blood cells or hemoglobin in the 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 "to fornicate" and originally meant only the illegitimate offspring of a purebred animal. Over time, in biology this word was supplanted 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., biology teacher at secondary school No. 3, Tver
2. Lesson “Introduction. Biology is the science of life” Titorov Yu.I., biology teacher, director of the KL in Kemerovo.
3. Lesson “Biology - the science of life” Nikitina O.V., biology teacher at Municipal Educational Institution “Secondary School No. 8, Cherepovets.
4. Zakharov V.B., Kozlova T.A., Mamontov S.G. “Biology” (4th edition) -L.: Academy, 2011.- 512 p.
5. Matyash N.Yu., Shabatura N.N. Biology 9th grade - K.: Geneza, 2009. - 253 p.

Edited and sent by Borisenko I.N.

We worked on the lesson

Borisenko I.N.

Konstantinova E.A.

Titorova Yu.I.

Nikitina O.V.

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

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Biology

“Research methods in biology” - History of the development of biology as a science. Planning an experiment, choosing a technique. Lesson plan: To solve what global problems of humanity requires knowledge of biology? Topic: Borderline disciplines: Assignment: Morphology, anatomy, physiology, systematics, paleontology. The meaning of biology." Biology is the science of life.

“Scientist Lomonosov” - Emphasized the importance of exploring the Northern Sea Route and developing Siberia. November 19, 1711 - April 15, 1765 (53 years old). June 10, 1741. Discoveries. He developed atomic and molecular concepts about the structure of matter. Ideas. Excluded phlogiston from the list of chemical agents. Job. Being a supporter of deism, he viewed natural phenomena materialistically.

"Botanist Vavilov" - All-Union Institute of Applied Botany. In 1906, Nikolai Ivanovich Vavilov. In 1924 Completed by: Babicheva Roxana and Zhdanova Lyudmila, students of grade 10B. 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.

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“Science of Living Nature” - Design of workbooks. 3. Biology - the science of living nature. 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 organic substances in the light, releasing oxygen. Question: What does biology study?

“Mathematics in biology” - “Identification of flat feet.” Reading graphs. The concept of symmetry; Types of symmetry. The concept of a graph of a function. General biology, 10th grade. “Construction of a variation series and a curve.” There will be ears at the points of contact. Circle, oval. There is a generally accepted point of view according to which mathematics belongs to the exact sciences. Proportionality.

There are a total of 14 presentations in the topic

Life sciences follow a path from large to small. More recently, biology described exclusively the external features of animals, plants, and bacteria. Molecular biology studies living organisms at the level of interactions of individual molecules. Structural biology - studies processes in cells at the atomic level. If you want to learn how to “see” individual atoms, how structural biology works and “lives,” and what instruments it uses, this is the place for you!

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 Biomolecules is to get to the very roots. We don't just tell you what new facts the researchers discovered - we talk about how they discovered them, we try to explain the principles of biological techniques. How to take a gene out of one organism and insert it into another? How can you trace the fate of several 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 section the most important, most modern biological techniques. To make it more interesting and clear, we heavily illustrated the articles and even added animation here and there. We want the articles in the new section to be interesting and understandable even to a casual passerby. And on the other hand, they should be so detailed that even a professional could discover something new in them. We have collected the methods into 12 large groups and are going to make a biomethodological calendar based on them. Stay tuned for updates!

Why is structural biology needed?

As you know, biology is the science of life. It appeared at the very beginning of the 19th century and for the first hundred years of its existence it was purely descriptive. The main task of biology at that time was considered to be to find and characterize as many species of different living organisms as possible, and a little later - to identify family relationships between them. Over time and with the development of other fields 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 by the appearance of the organism or the relative position of its internal organs. Finally, quite recently (in the 50s of the last century) such a field of knowledge as structural biology- a science that studies processes in living organisms at the level of change spatial structure individual macromolecules. Essentially, structural biology is at the intersection of three different sciences. Firstly, this is biology, because science studies living objects, secondly, physics, since the widest arsenal of physical experimental methods is used, 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 "L", and that the ribosome has a large and small subunit consisting of proteins and RNA in a specific conformation.

Global goal structural biology, like any other science, is “to understand how everything works.” In what form is the chain of the protein that causes cells to divide folded, how does the packaging of the enzyme change during the chemical process that it carries out, in what places does 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 (on an as yet unstudied object) can be answered on a computer without resorting to an expensive experiment.

For example, you need to understand how the bioluminescence system in worms or fungi works - they deciphered the genome, based on this data they found the desired protein and predicted its spatial structure along with the mechanism of operation. It is worth recognizing, however, 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 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 this is 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 well-known double helix from a vintage construction set. 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 (muscle fiber protein) of the sperm whale (Fig. 3). It looked, of course, not 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 construction set.

Ten years later, in 1984–1985, the first structures were determined by nuclear magnetic resonance spectroscopy. Since that moment, several key discoveries have occurred: in 1985, the structure of the first complex of an enzyme with its inhibitor was obtained, in 1994, the structure of ATP synthase, the main “machine” of the power plants of our cells (mitochondria), was determined, and already in 2000, the first spatial structure was obtained “factories” of proteins - ribosomes, consisting of proteins and RNA (Fig. 6). In the 21st century, the development of structural biology has advanced 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, immune system proteins, and many others.

With the advent of new cryoelectron microscopy imaging and imaging technologies in the 2010s, many complex super-resolution structures of membrane proteins have emerged. The progress of structural biology has not gone unnoticed: 14 Nobel Prizes have been awarded for discoveries in this field, five of them in the 21st century.

Methods of structural biology

Research in the field of structural biology is carried out using several physical methods, of which only three make it possible to obtain the spatial structures of biomolecules at atomic resolution. Structural biology methods are based on measuring the interaction of the substance under study with various types of electromagnetic waves or elementary particles. All methods 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). Back in the early 20th century, it was discovered that by using the X-ray diffraction pattern on crystals, one can study their properties - the type of symmetry of the cell, the length of bonds between atoms, etc. If there are organic compounds in the crystal lattice cells, then the coordinates of the atoms can be calculated, and, therefore, , chemical and spatial structure of these molecules. This is exactly 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, you need to somehow obtain crystals, and their size must be large enough (Fig. 8). While this is feasible for not very complex molecules (remember how table salt or copper sulfate crystallizes!), protein crystallization is a complex task that 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, based on the obtained data (“raw” diffraction patterns; Fig. 8), the structure needs to be “calculated”. Nowadays this is also a routine task, but 60 years ago, in the era of lamp technology and punched cards, it was far from 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 not always the case.

And fourthly, crystal is far from the natural state of protein. Studying proteins in crystals is like studying people by cramming ten of them into a small, smoky kitchen: you can find out that people have arms, legs and a head, but their behavior may not be exactly the same as in a comfortable environment. However, X-ray diffraction is the most common method for determining spatial structures, and 90% of the PDB content 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 usually a single 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 resulting crystals. You can read more about these romantic studies in the article “ Laboratory for Advanced Research of Membrane Proteins: From Gene to Angstrom» .

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

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

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

Passing through the undulator, electrons begin to periodically deviate from the direction of the beam, experiencing acceleration and emitting X-ray radiation. 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 an ultra-powerful and very short flash (lasting 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), but in those few femtoseconds while the crystal is intact, the highest quality images can be obtained due to the high intensity and coherence of the beam. The cost of such a laser is $1.5 billion, 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. Conversion of proteins into plasma in 50 fs under the influence of a free electron laser pulse. Femtosecond = 1/1000000000000000th of a second.

Using NMR spectroscopy, about 10% of the spatial structures in the PDB have been determined. In Russia there are several ultra-high-power sensitive NMR spectrometers, which carry out world-class work. The largest NMR laboratory not only in Russia, but throughout the entire space east of Prague and west of Seoul, is located at the Institute of Bioorganic Chemistry of the Russian Academy of Sciences (Moscow).

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

Video. 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 the “reverse” signal - oscillation of the magnetic moment of the sample. To increase sensitivity by 2–4 times, the sensor is cooled to a temperature of −200 °C, thereby eliminating thermal noise. To do this, they build a special machine - a cryoplatform, which cools helium to the required temperature and pumps it next to the detector.

There is a whole group of methods that rely on the phenomenon of light scattering, X-rays or a neutron beam. These methods, based on the intensity of radiation/particle scattering at various angles, make it possible to determine the size and shape of molecules in a solution (Fig. 16). Scattering cannot determine the structure of a molecule, but it can be used as an aid to 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, which can produce a beam of neutrons or a powerful stream 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 while emitting light of another wavelength. You can select a pair of compounds, for 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 required wavelength and measure the fluorescence of the acceptor. The FRET effect depends on the distance between molecules, so if you introduce a fluorescence donor and acceptor into the molecules of two proteins or different domains (structural units) of the same protein, you can study interactions between proteins or the relative positions of domains in a protein. Registration is carried out using an optical microscope, so FRET is a cheap, albeit low-informative method, the use of which is associated with difficulties in interpreting the data.

Finally, we cannot fail 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 laws of behavior of molecules to simulate the behavior of a protein in a computer model. For example, using the molecular dynamics method, you can monitor in real time the movements of a molecule or the process of “assembling” a protein (folding) with one “but”: the maximum time that can be calculated does not exceed 1 ms, which is extremely short, but at the same time requires colossal computational resources (Fig. 18). It is possible to study the behavior of the system over a longer period of time, but this is achieved at the expense of an unacceptable loss of accuracy.

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

The main field of practical application of the results of structural biology is drug development or, as it is now fashionable to say, drag design. There are two ways to design 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 protein-drug complexes have been obtained, you can create a model of the “ideal drug” in accordance with the properties of the binding “pocket” on the surface of the protein molecule, identify the necessary features of the potential drug, and search among all known natural and not so known compounds. It is even possible to build relationships between the structural properties of a 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. This means that of all the known molecules, you need to find the compound with the largest charged bow.

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

The general trend in biological research is increasingly leaning towards not only qualitative, but also quantitative descriptions 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

1. Bioluminescence: Rebirth;
2. The triumph of computer methods: prediction of protein structure;
3. Heping Zheng, Katarzyna B Handing, Matthew D Zimmerman, Ivan G Shabalin, Steven C Almo, Wladek Minor. (2015).