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I didn’t cover this variable because most photographers don’t change their camera body to control the depth of field. I mention this if you compare images with a friend with a different camera body.

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Generally, an f-stop of f/2.8 has a blurrier background than an f-stop of f/16. If you want to create a shallow depth of field, select a wide aperture. Select a smaller aperture if you want more of the scene in focus.

If you’re aiming for a deep depth of field, you may need to figure out exactly where your focus point should be. You can figure this out by calculating the hyperfocal distance.

But with a 200mm focal length, my focus area would start at 9.68 ft (2.95 m) and extend to 10 ft (3.05 m). This is a much shallower depth of field. Only 3.94 inches (10 cm) will be in focus!

If you are taking a portrait, a very wide aperture like f/1.2 can put the eyes in focus while the nose and ears are blurry. Using the same f-stop, you can focus on the nose, but this will blur the eyes.

According to a report by BiopharmaTrend, about 45% of all drug discovery start-ups that use or develop specialized AI tools are focused on small molecules, while only about 24% are working to develop biologic drugs. The figures are similar for the cash being invested in these firms by venture capitalists.

These long molecules might not look like the small-molecule drugs of the past, and they don’t have the characteristics that traditionally make a good small-molecule drug. But clinical trials have shown that the molecules can get into cells and effectively treat different cancers.

And it’s not just proteins that can be targeted. A key area of small-molecule research is the identification and development of molecular entities capable of targeting RNA. For a long time, human RNA was thought to be undruggable, but researchers now know that RNA assumes 3D structures, creating binding sites for small molecules to interact with.

F-stop

You have three options for decreasing your depth of field. You can widen your aperture by decreasing the f/stop number, moving closer to your subject, or using a longer focal length.

You can use this mode to get a blurred background, even if you’re not shooting portraits. The original settings of the first photo on the left were 9.0mm, f/2.8, 1/121 s, and ISO 32. Clicking the edit button gives you some options to change the aperture.

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Deep and shallow depth of field fall on a continuum. You can set your aperture for an entirely sharp scene or have a very small line of focus. It’s up to you. Most photographers find a sweet spot somewhere in the middle.

Small molecules are often effective and cheap, especially once they come off patent. And they can be easier than biologics to store and take as a patient. As researchers understand more about how diseases and drugs work at a molecular level, older molecules whose mechanisms were perhaps not understood when they were first developed can become useful once more.

Matthew Disney is a chemist at at the Herbert Wertheim UF Scripps Institute for Biomedical Innovation and Technology at the University of Florida who founded Expansion Therapeutics to develop small molecules to bind to RNA structures. He has also noticed the trend toward larger molecules. “FDA-approved drugs are getting larger in size,” Disney says. “Industry putting things out in the literature to sort of show that these bigger molecules can be orally bioavailable—I think it just makes the science better for everybody.”

Newer iPhones make it easier to control the effect. I still can’t change the aperture on my iPhone 11S, but I can simulate and control shallow depth of field.

One company working on RNA binding is Arrakis Therapeutics, cofounded by chemist Jennifer Petter. She says the firm is working on multiple approaches for silencing RNA, including binding a regulatory section to modify biology directly, inducing RNA degradation, and even covalently binding the polynucleotide. “Within our walls, we actually have a multimodality small-molecule shop,” she says.

No one expects computers to replace medicinal chemists, but many scientists think AI can help them. Several drug discovery companies with AI-powered platforms have recently progressed molecules to the clinic, sometimes faster and cheaper than might be expected with other techniques.

If you’re not getting the depth of field you want, the next thing to change is relative distance. You can try getting closer to your subject. If that doesn’t help, move your subject away from the background.

A 200mm focal length gives you a field of view of about 10 degrees. A 50mm focal length gives you a field of view of 40 degrees. That’s a very different composition.

In the image below, only the foreground is in focus. The background gives a sense of the environment without distracting from the foreground. The foreground flowers are in focus, while the background of the garden is blurred.

First, I enter my camera (Sony a7R IV—because sensor size affects DoF. Then, I enter the focal length of my lens, which is a 50mm lens set at f/11. Lastly, I put in how far away I am from my subject, about 9.84 ft (3 m).

This is one reason portrait photographers prefer apertures of f/1.4 to f/5.6. It’s also why landscape photographers prefer apertures from f/11 to f/22. But that’s not all there is to it. Other details factor into how wide or narrow your depth of field is.

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Depth of field in photography describes how much of the scene is in focus. More specifically, DoF is the distance between the closest and farthest points of the image that are in focus.

Understanding depth of field is crucial. It empowers you to manipulate focus creatively, which leads to captivating images. Mastering this concept lets you intentionally control sharpness and blur.

A shallow depth of field is a great way to separate the foreground from the background. This technique is good when the background is uninteresting or distracts attention from the subject.

At one stage, small-molecule drugs seemed at risk of going out of fashion, as industry began to favor biotherapeutics. But over the past 10 years, small molecules have made it clear that they aren’t going away. New classes of molecules, such as proteolysis-targeting chimeras (PROTACs) and molecular glues, have people excited. So do technologies, such as machine learning and generative artificial intelligence, that are helping drive drug discovery. Today, drug hunters have more ambition to go after difficult targets and to use novel chemistry. And that makes it an exciting time for chemists.

To do this, you use a shallow depth of field, meaning your foreground is in focus, but the background is not. This is also called bokeh.

depth offield中文

The portrait below has a shallow depth of field. Notice the near eye (left) is in focus, but the back eye (right) is blurred. To get both eyes and nose in focus, you would need to use a narrower aperture (larger f-number).

The focal length of a lens also affects the DoF. Without getting too complex, a longer focal length, like 300mm, gives you a shallower depth of field than a 35mm wide-angle lens.

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This article was updated on Oct. 31, 2023, to correct Matthew Disney’s affiliation. He is based at the Herbert Wertheim UF Scripps Institute for Biomedical Innovation and Technology at the University of Florida, not Scripps Research.

Three elements change how much of the scene is in focus. These are aperture, focal length, and relative distance. Once you know how to control the depth of field, you can decide how deep or shallow you want your focus to be.

Imagine looking out into a landscape through your camera. Depth of field starts at the closest in-focus object and ends at the farthest in-focus object.

Covalent drugs can grab hold of reactive amino acids on proteins, even when a suitable pocket, or keyhole, does not exist. One high-profile example is the work of Kevan Shokat of the University of California, San Francisco, and his team. In 2013, Shokat’s group found a way for a drug to covalently bind to a cysteine in a cancer-causing mutant of KRas and inhibit the protein. Today, it’s not just cysteines that can be targeted but many other reactive amino acid side chains as well.

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When you adjust one setting on your camera, you’ll need to adjust the other two to get the correct exposure. You can learn everything you need about how to do this with the exposure triangle.

Remember, it’s extremely difficult to create a blurred background if your subject and the background are too close. Creating the depth of field you want is all about depth relationships.

No PROTACs have yet jumped over the final regulatory hurdles and won approval. But experts say the induced-proximity concept has proved its naysayers wrong and that it’s just a matter of time before such a drug makes it to market.

Biotech entrepreneur Ethan Perlstein, who is trying to repurpose existing small molecules to treat metabolic disorders, contends that the golden age never ended—people just got distracted by other therapeutic modalities. There is an element of fashion to research, and “small molecules is a terrible term for marketing,” he says.

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Today, small molecules can do many of the same things that biologic drugs can do and find financial success doing so. For example, among the drugs that treat spinal muscular atrophy are Zolgensma, a onetime gene therapy injection; Spinraza, an antisense oligonucleotide given as an injection into the spine every few months; and, since 2020, a daily small-molecule treatment Evrysdi (risdiplam) given as an oral solution. Evrysdi racked up over $1 billion in sales in 2022, and its sales in the first half of this year grew by 48% from the same period in 2022, while sales of Zolgensma and Spinraza fell.

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These new synthetic tools give medicinal chemists more options and can help them build on molecules that are shown to bind to a target but perhaps not so well. “Combining these with the prevalence of covalent molecules and the prevalence of degraders opens up things that you can do with molecules,” Todd says.

Unlike landscape photographers, portrait photographers don’t necessarily want the entire scene in focus. If you’re taking street portraits, you want the person to be the main focus and an out-of-focus background to minimize distractions.

The DoF calculator also tells me the hyperfocal distance. This is important for landscape photographers. Hyperfocal distance tells me where to focus in the scene to get a sharp focus to infinity. (Infinity is as far as the eye can see.)

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Today, medicinal chemists are making larger and larger molecules. Called beyond-rule-of-5 molecules, these can include bifunctional drugs like PROTACs as well as much larger molecules, such as cyclic peptides. “So what is small anymore?” Barrish asks.

Macro photographers use long macro lenses to capture small subjects like flowers and insects. These lenses let photographers get very close to their subjects.

Meanwhile, molecular glues are smaller ways to induce degradation using ubiquitination. They work by glomming on to one protein to change its affinity for another protein in the cell.

Depth of fieldcalculator

Our eyes are drawn to the in-focus area of a photo. So, as a general rule, you should focus on the point of greatest interest. Depth of field tells you how much of the scene is in focus in front of your focal point. It also tells you how much of the background is in focus.

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Finally, the focal length of your lens also impacts the DoF. If you have a zoom lens, try a with less zoom for a greater depth of field. Changing the focal length also affects your composition. So, balancing the perfect DoF with the perfect frame is best.

Rather than losing their attractiveness in the modern world of biological advances, small molecules are having something of a renaissance. There’s a buzz and a feeling that medicinal chemists can design solutions for diseases they once would have considered impossible to confront.

Landscape photographers often want the entire scene in focus, from the closest rock to the farthest mountain. This is a “deep” depth of field. In the landscape image below, there is a deep DoF. The waterfall in the background and the trees and rocks in the foreground are in focus.

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I’ll show you how to achieve deep and shallow depth of field. But there’s one more thing you need to know about the focus area.

It is possible to combine a shallow and deep depth of field in one photo. The photo below cleverly uses a smartphone to capture a wide DoF in the image. Then, they photographed the image on the phone using a shallow depth of field.

I’ll finish our article by introducing you to some topics related to depth of field. Focus stacking is a way of creating a very deep DoF. It is also possible to simulate a shallow depth of field. This is particularly useful when using a smartphone.

But because they are close to their subjects with long-focal length lenses, the depth of field is often very shallow. You can see this in the close-up of spoons on a textured background below.

“My personal opinion is that the next big thing is nucleic acids,” says Zoë Waller, an associate professor in drug discovery at University College London. “Targeting nucleic acids was a specialist area, but it is really becoming more mainstream now.”

If you want to take advantage of a narrow depth of field, you need distance between the subject and background. For instance, if your model stands against a wall, you can’t blur the wall. The model and the wall are on the same plane of focus. So, ask your model to step towards you.

“That’s where the golden opportunity arises: that we can have a renaissance with better small molecules with AI coming in,” UCL professor Waller says.

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Not too long ago, these small-molecule drugs looked as if they were going out of fashion. Advances in biotechnology enabled pharmaceutical companies to cost-effectively generate a range of biologics, such as large peptides, recombinant proteins, monoclonal antibodies, antibody-drug conjugates, fusion proteins, and vaccines.

Petter agrees. “If you’re willing to take on the larger molecules, this opens up the possibility for some really remarkable, innovative molecular designs,” she says.

We talk about depth of field in terms of “deep” and “shallow.” Deep depth of field is also called “wide” or “large.” Shallow depth of field is also called “small” or “narrow.”

Depth of field (DoF) refers to how much of your scene is (and isn’t) in focus. Photographers often manipulate the depth of field as a creative choice. They do this by selecting the right aperture for the scene they want to create.

With a wide-angle lens, you can equalize the compositions by walking closer to your subject. Doing this makes the difference in depth of field less noticeable.

There is one instance where your DoF can be manipulated. That is by using a tilt-shift lens. By playing around with the “tilt” of a lens, you can place an entire scene in focus when using a wide aperture.

These modular building blocks, and the ways they have been described computationally, also primed researchers to experiment with how to use artificial intelligence and machine learning to help design new drugs. Historically, computational methods helped drug hunters and builders model new small-molecule therapeutics without actually having to synthesize them. That trend has continued with AI-driven start-ups, which are either solely or partially focused on small-molecule drug discovery.

Molecular-glue firms are now signing deals with Big Pharma. For example, Proxygen has inked deals with both Merck KGaA and Merck & Co. to develop molecular glues as degraders in the last year. And Monte Rosa Therapeutics’ latest collaboration is with pharma firm Roche to develop glues against cancer and neurological disease targets previously thought undruggable.

“If you would have told medicinal chemists 15, 20 years ago that we’d be doing chemistry in cells, we would just laugh at that, but that’s what we’re doing,” says Joel Barrish, an industry veteran now at RA Capital Ventures. “I mean, we are basically taking control of the natural regulatory mechanisms.”

Aperture

I enter my camera body (Sony a7R IV) and 50mm lens. But this time, I’ll put f/2.8 instead of f/11. To be consistent, I’ll keep my subject’s distance at 9.84 ft (3 m).

With landscapes, if you focus on the foreground, the background appears blurry. If you focus on the background, the foreground looks out of focus. To fix this, the focus needs to be somewhere in the middle between the foreground and background. This focus point is the hyperfocal distance.

Your sensor size also affects the depth of field. Larger sensors have a shallower DoF. So, a crop sensor camera (APS-C sensor) generally has a narrower depth of field.

And the chemists involved need new synthetic methods to add to their tool kits, according to Matthew Todd, who builds open-source medicinal chemistry projects in his academic lab at University College London. One such development is the skeletal editing techniques that can swap atoms in and out of molecular structures. A recent example can swap a carbon out for a nitrogen in an aromatic ring.

Choosing the right depth of field affects all types of photography, from portraits to landscapes. Continue reading to understand depth of field and how to use it in your photos.

The pharmaceutical industry is over 100 years old, and for many, the true golden age of drug discovery ran from the 1940s to the 1970s. Small-molecule drugs from this era, such as antidepressants, antipsychotics, and oral contraceptives, were truly revolutionary. Instead of calling today the golden age, chemists are using different terms: a new golden age, a new age, a renaissance, or a renewal.

Notice that the DoF in front and behind my subject changes a lot. With an aperture of f/11, my DoF was 9.32 ft (2.84 m). With f/2.8, only 1.97 ft (0.6 m) will be in focus. It’s a much narrower range.

Another change has been the externalization of services, such as compound library design. The proliferation of contract research organizations and other service firms means that biotechs can buy the chemical expertise they need rather than have to develop it themselves. And those firms can also drive technological innovation—for example, by building DNA-encoded libraries or on-demand compounds.

To combat both situations, photographers use a technique called focus stacking. They take many images of a scene and change the focal point slightly with each image.

The aperture setting is the easiest way to control DoF. Generally speaking, the wider the aperture, the shallower the depth of field. But opening up the aperture lets in more light. You may need to balance the increased light with a faster shutter speed.

Industry insiders point out that chemists would not be making these strides without advances in biology and instrumentation. “It’s advancements of science, overall,” RA Capital Ventures’ Barrish says. “It’s advancements in chemistry and technologies that really are allowing us to begin to access [targets and biology] that we hadn’t been able to do before.”

Genetic screening also helped medicinal chemists’ efforts by finding new links between genes and diseases so that drug hunters could identify new drug targets. And perhaps unsurprisingly, Petter says that improvements in genetic sequencing have hugely helped her work developing RNA-targeting molecules.

If your phone’s camera doesn’t have this feature, photo apps like Focos for iPhone simulate depth of field. Apps like this change the aperture virtually. Using the Focos app, we created an image that simulated an f/20 aperture (middle photo) and f/1.4 (right)

Changing the depth of field in photography is a great technique all photographers should know. To increase your depth of field, you have three options. You can narrow your aperture by increasing the f-stop number, moving further away from your subject, or using a shorter focal length.

Twenty-five years ago, Christopher A. Lipinski created a set of rules, or guidelines, to describe the characteristics of successful small molecules that could be taken orally. Dubbed the rule of 5, they were based on observations that successful drug candidates were often smaller than 500 g/mol in mass and lipophilic. But not all the drugs being developed by medicinal chemists fit those criteria, nor have they ever.

Depth of field has much to do with distance—but relative distance rather than absolute distance. Moving farther away from your subject gives a greater DoF. In contrast, moving closer gives a shallower DoF.

When you select a focal point, the focus isn’t equally distributed in front of and behind this point. Most of the time, one-third of your focus falls in front of your focal point and the other two-thirds behind it.

Compare these two images below, taken from the same vantage point. The only setting that changed was the focal length. The first image was taken at 133mm, and the other image was taken at 100mm. Notice the change in blur in the waterlilies in the background.

As drug hunters gaze into their crystal balls, small molecules are still a key part of the medicinal arsenal. But perhaps more and more, what those molecules look like will change. “I envision there will be types of drugs that will look weird to us because they don’t look like what we’re expecting,” Waller says. “And that’s what we need. . . . There’s so much potential there.”

Developing those larger molecules requires medicinal chemistry. “I don’t think you can make medicine without organic chemists. Both academic and industry,” Disney says. “You need the academics to make new methods and industry to deploy them. You need synthetic people in addition to chemical biologists, bioinformatics, and biologists.”

Smartphones are limited in their ability to create blurred backgrounds. But you can still achieve the effect by getting close to your subject or using a depth-of-field simulator app.

The biggest change, experts say, is the possibilities opened up by covalent inhibitors and induced-proximity molecules, molecules that go beyond the lock-and-key approach to targeting unwanted proteins.

Now that I’ve introduced you to the DoF calculator, play with it a bit. Enter your camera body and focal lengths to see how the numbers change. Many factors control the depth of field.

The DoF calculator (image below) says the nearest point in focus is 7.05 ft (2.15 m) away. The furthest point in focus is 16.37 ft (4.99 m).

This calculator also tells me that 2.79 ft (0.85 m) in front of the subject will be in focus (30.07%). Six feet and 5 inches (2 m) behind my subject (69.93%) will be in focus. This is roughly one-third versus the two-thirds I mentioned above.

First, I enter my camera body (Sony a7R IV) and choose f/8. To be consistent, I’ll keep my subject’s distance at 10 ft (3 m). I’ll first enter 50mm as the focal length of my lens, then change it to 200mm.

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Let me give you an example. I will use PhotoPill’s online depth of field calculator to compute how far in front of and behind a subject will be in focus. It might help to open the calculator yourself and follow along.

Looking back, Hornberger says, these developments came from the careful structural work of chemical biologists like Shokat. This work helped medicinal chemists move away from the lock-and-key paradigm of protein inhibition. Today, many medicinal chemists are looking for different toeholds and ways to alter protein behavior.

The depth of the field isn’t affected by just one setting on your camera. As we’ve shown, you can change three variables to affect the depth of the field. These are aperture, focal length, and relative distance.

F-number

Changing your aperture (f-stop) is one of the best ways of changing the DoF. Generally, the wider the aperture, the shallower the depth of field, and vice versa. Remember that wide apertures have small f-numbers.

Last year, sales of the 10 top-selling drugs were split 40:60 between small molecules and larger, more complicated biologics, according to Drug Discovery and Development. But those numbers are skewed by the huge cost of some biologic blockbusters. On a global scale, around 90% of all drugs sold are small molecules, according to a Medicine in Drug Discovery paper (2021, DOI: 10.1016/j.medidd.2020.100075).

The services from these molecule-on-demand firms have “really altered things,” Todd says. “We’ve been looking at all the molecules that you can buy, and we’re trying to think of ways of expanding that by synthesizing new core building blocks, which you can then decorate with other things that you can buy.”

Chemists have also since extended the approach to create a host of variants. These include regulated induced proximity targeting chimeras (RIPTACs), which hold on to, stabilize, and inhibit problem proteins, and lysosome-targeting chimeras (LYTACs), which specifically mark extracellular proteins for destruction. These molecules draw together proteins involved in cancer to cause cell death or pull extracellular proteins into the cell for destruction. Chemists can also now create molecules that try different posttranslational modifications, such as deubiquitination, phosphorylation, and acetylation.

And the most well-known examples of induced-proximity targeting are the proteolysis-targeting chimeras, or PROTACs, first developed by Craig Crews’s laboratory at Yale University. These floppy molecules with binders at both ends can draw together two proteins in a cell and add ubiquitin tags to flag the protein of interest for degradation.

Shallowdepth of field

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Depth of fieldsimulator

Let’s give you an example. Here is a portrait of a cat taken with an iPhone. When you select Portrait mode, the camera automatically applies a background blur to the image.

And drug developers are learning new ways to use small molecules to target disease. The traditional approach to drugging many diseases was to find a molecular key that could fit inside a protein, blocking off part of its 3D shape and inhibiting its activity. Increasingly, researchers are instead using small molecules to covalently bind to proteins or to bring proteins near one another so they can work together.

The top highlights DoF when using an aperture of f/2.8. The girl is in focus, but the dog in the foreground and the tree in the background are blurry.

There are situations where it is impossible to get a deep enough depth of field in one image. Landscape photographers sometimes struggle with this. They may find it hard to focus on a close foreground element while keeping distant elements in focus.

It’s possible to simulate a shallow depth-of-field effect digitally. You can add a blur effect in Photoshop or use apps or editing software that digitally simulate the effect.

But there’s a bit more to it than that. A 200mm lens focused at 9.8 ft (3 m) doesn’t show you the same composition as a 50mm lens focused at the same distance.

But organic compounds with low molecular weight—molecules that can be administered orally and can pass through cell membranes to reach intracellular targets—have been a mainstay of the pharmaceutical industry for over 100 years. Rather than fade away, they continue to be an important part of the industry’s therapeutic arsenal. In the past 10 years or so, advances in technology, synthetic methodology, and biopharmaceutical research have opened up more opportunities for innovative and creative small-molecule drugs.

A landscape photographer may take three or more images. The first focuses on the foreground element, the second on the midground, and the third on the background.

Many chemists would agree that there is a renewed enthusiasm for what medicinal chemists can do, even if they wouldn’t call it a golden age. Keith Hornberger, who leads a team of medicinal chemists at the biotechnology firm Arvinas, says golden age is not the right moniker. “I’d say it’s the new age,” he says. New uses for small molecules are ones that were never considered 20 years ago and have redefined what chemists think of as druggable.

Those technological leaps began in the 1980s with improvements in structural biology, including the development of cryo-electron microscopy and high-resolution X-ray crystallography techniques that allow scientists to visualize biology in atomic detail. But they also involve the bioinformatic screens and assays that can test for places where a protein can interact with another protein.

With a 50mm focal length, my focus area would start at 7.68 ft (2.34 m) and extend to 13.71 ft (4.18 m). Everything within this 6.03 ft (1.84 m) range will be in sharp focus.

Data from the US Food and Drug Administration show that small molecules continue to play a vital role in the pharmacopoeia. Of the 293 new chemical entities that the FDA approved in 2017–22, 182 were small-molecule drugs.