Combinatorial vs. Enumerated Simplified

Combinatorial vs. Enumerated
Simplified with Burgers

When faced with many options, whether it's burgers or chemical compounds, there are two ways to choose the right one: combinatorial or enumerative. Let’s dive into these concepts using our favorite bite—burgers! By the end, you'll understand why the combinatorial approach is a game-changer in both the kitchen and drug discovery.

The Enumerated Approach

Picture this: a menu listing every possible burger combo—classic cheeseburger, bacon double, veggie with avocado, and so on. While it covers all the basics, the menu quickly becomes large and confusing.

For example, if you have 10 types of patties, 15 toppings, and 5 sauces, your menu could theoretically list 750 different burgers! —Why spend time choosing options you might not even like?

The Combinatorial Approach

Instead of listing every possible burger, what if the menu simply had a list of ingredients and rules for combining them?

You will end up with categories like sauces, patties, and toppings. When you order, a chef will create the burger on the spot based on your choice of ingredients. This way, you don’t need to stare at a giant menu—just the building blocks.

With this approach, those same 10 patties, 15 toppings, and 5 sauces can be combined into those 750 unique burgers on demand, giving you the flexibility to order endless options without the wasted time—now that’s Combinatorics at work!

Why the Combinatorial Approach Wins Every Time

Flexibility and Efficiency. The combinatorial approach allows for almost infinite possibilities efficiently. It’s easier to explore different options and cater to unique preferences without overwhelming the discovery process.

This method is not just great for burger joints; it’s also relevant in important fields like Medicinal Chemistry, where managing potential drug candidates can become a painful task. In fact, with the Combinatorial Approach you can explore millions of compunds using just a few building blocks, drastically cutting down the processing time and resources needed for research.

Chemical Spaces: Sources for Unlimited Burgers

In the realm of medicinal chemistry, scientists often navigate vast "Chemical Spaces"—abstract, conceptual environments where every possible chemical compound is a point within this Chemical Space. These Spaces can be incredibly large, containing billions or even trillions of potential compounds.

To manage this immense diversity, scientists use computational methods to explore these Spaces efficiently, much like how combinatorial approaches can simplify choosing the perfect burger. Rather than searching through every possible compound (akin to searching through an exhaustive list of burgers), researchers focus on strategic combinations of molecular building blocks.
This approach dramatically reduces the complexity and time needed to identify promising drug candidates within the vast Chemical Space.

FAQs

"Do I miss out on some burgers?"

You don't. While the combinatorial approach is way faster, it still does not miss out on anything. The best scoring compounds will emerge at the top as if you screened an enumerated library. The results are retrieved without any compromises.

"What if my exact match is not covered?"

Searching inside Chemical Spaces will provide you with the most similar compounds based on the needs of the projects. If the exact molecule is not inside the Space, closest alternatives will be retrieved.
Think of a cheeseburger: If cheddar is not an available ingredient, options with mozarella, swiss or monterey jack will be suggested.

"How do I get my burger?"

We collaborate with burger restaurants (= chemical compound suppliers) to create Chemical Spaces. Whatever result is of interest to you can be ordered and delivered to your table. More restaurants also means greater diversity and options of ingredients, resulting in a wider range of potential combinations.

Obviously, it is also possible to make the burger yourself! Just use the ingredients and combine them.

"What similarity is used to search for results?"

There are many ways to screen for something similar: "I want to search for burgers that have a similar flavor profile", "I want only vegan options", "I want to see all options with beef". Based on the direction of what you want, most similar options matching your request are retrieved.

"Can I get your burgers from my pizza place?"

No. Our concept of searching in large numbers for the best burgers is bound to our technology. Others cannot process our combinatorial Chemical Spaces or screen those. Yet, it is possible to apply our methods to mine for the burgers and use them afterwards in your own scenarios.

"Can I search for burgers with my own ingredients?"

You can set up a combinatorial Chemical Space by yourself and use it to screen it. This way you can use your own ingredients and rules how to combine them to create solutions that only you can make.

FAQs

FAQs, but Sciency

"Do I miss out on some molecules?"

The applied methods are exhaustive: All compounds inside the Chemical Space are assessed for their overall similarity to the query molecule without comprising on the completeness of the results. The scoring system ranks compounds by similarity, with the most similar at the top and the least similar at the bottom. As more results are generated, all of them are ranked according to relevance.

"What if my exact match is not covered?"

Our search methods retrieve compounds based on their similarity to the template molecule. Regardless of whether an exact match is found (with the exact match always emerging as the top hit), the most similar compounds will be presented as results. These results may contain smaller modifications or additional decorations in their structure, but they represent the best possible solutions according to the algorithm's analysis.

"How do I get my compounds?"

Results retrieved from Chemical Spaces are accessible and synthesizable per design. We collaborate with compound suppliers in the generation of their own Chemical Spaces. Compounds retrieved from those are commercially available and can be made on demand at competitive pricing. The approach guarantees high success rates and fast delivery times.
As robust chemical reactions are used to create those Spaces, it is also possible to purchase the building blocks and synthesize the compounds by yourself.

"What similarity is used to search for results?"

Several methods are available to screen Chemical Spaces for similar compounds: fuzzy pharmacophores, molecular fingerprints, and substructure matching.
Each of these methods retrieves different types of similar compounds, enabling targeted screening for molecules tailored to a specific drug discovery challenge. Additional settings allow you to fine-tune your results further.

"Can I screen Chemical Spaces with other technologies?"

No. The file format of combinatorial, ultra-large Chemical Spaces (.space) is not supported by other software. Our search algorithms were developed to efficiently mine for compounds in this environment and are the only way to access the compound collections.
It is possible to use our search methods via GUI or CLI to enumerate the results in a common format (e.g., .sdf) and then subsequently use them in other applications for postprocessing.

"Can I search for compounds with my own building blocks and reactions?"

Yes, it is possible to create your own Chemical Space with your own building blocks and in-house reactions. This approach will set up a searchable compound collection of synthetically accessible molecules that covers all possibilities that you can realize in your own lab.
Chemical Spaces share only a very small overlap. Therefore, it is always a good idea to work with your resources to tap into unexplored regions of the chemical space.

FAQs, but Sciency

More Insights

Chemical Spaces Search methods

The Chemical Space Navigation Platform

infiniSee helps you to conveniently browse through almost infinite options in the search for the best match to your request.
After loading your query, you retrieve the most relevant results from ultra-vast Chemical Spaces in a flash from your own hardware.

The three different search methods of infiniSee (fuzzy pharmacophores, molecular fingerprints, substructure matching) are also available as command-line tools.

Decided on which burger yet?
Start exploring now!

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