Drug Discovery Solutions

SBDD aims to answer which compounds are most likely to show biological activity at a target structure. This can happen through the further development of a compound or by predicting which molecules from a collection are most likely to bind to the target. The latter is called virtual screening and is one of the most reliable methods to identify new chemotypes for a target.

What makes us special?
Our software can be used by anyone, enabling everyone to fully unlock their potential. Both medicinal chemists without prior experience and computational chemists can quickly obtain scientifically sound results. In addition to standard tasks like docking and scoring, our software also helps generate ideas that one might not otherwise consider. Ultimately, it uses a range of innovative algorithms that perform with unmatched speed and can process resource-efficient numbers that would otherwise be out of reach.

The absence of a target structure may be frustrating, but it's not an absolute barrier to a drug discovery campaign. LBDD is a reliable method to still identify potential new binders by searching for related compounds to an active binder with known biological activity.

What makes us special?
With several decades of experience in Chemical Space exploration technology, we have developed numerous methods to search compound collections containing billions, trillions, or even more entries—referred to as Chemical Spaces—for similar molecules. Larger hunting grounds for drug-like compounds significantly expand the pool of options, thereby increasing their relevance for R&D.

The mere ability to process such vast numbers is already an innovation, but this is achieved with unprecedented speed: trillions of entries can be reliably screened within seconds, with results that are either synthetically accessible or even commercially available. The various similarity search methods further allow for project-specific searches, enabling the identification of the content most relevant to the project’s objectives.

Fragments essentially need just one thing to develop into drug candidates: better binding affinity. This can be achieved through the three aforementioned methods—growing, linking, and merging—by gradually introducing new functionalities into the molecule, which form additional interactions with the target structure. This represents the structure-based aspect of the optimization process.
Additionally, it is crucial to consider which compounds are commercially available that contain the fragment as a substructure. This allows for rapid and straightforward acquisition, enabling the quick establishment of structure-activity relationships (SARs).

Why are we special?
Our drug discovery solutions offer comprehensive support for all aspects of a fragment-focused drug discovery campaign. Iterative compound extensions can be performed efficiently and effortlessly, providing dependable approaches to enhance the potency of the compounds.

Additionally, we provide access to the largest compound catalogs through our Chemical Space exploration. Here, we’re talking about an increase from a few thousand compounds containing a specific fragment of interest in the largest available catalogs to millions or even billions in our combinatorial Chemical Spaces.

A song as old as time: A promising target involved in an important pathway or that is overexpressed in a cancer cell line emerges and becomes the hot topic in the scientific community. The race for finding molecules that can bind to the structure and modify its activity has begun. Here, speed and novelty are the key elements to success.

Learn how to discover novel chemotypes and drug candidates for your target by following this link.

The success of structure-based drug design hinges on the accurate prediction of a ligand's binding mode. By correctly anticipating the binding location and the involved residues, as well as determining the most likely binding orientation, researchers can optimize drug candidates and accelerate the drug discovery process by facilitating the next steps with informed decisions.

Our software helps you to detect potential binding sites at your target structure or complex. Read more about it following this link.

Sometimes it can be a blessing to find something, especially in a project with difficult targets with no known binders. Sometimes it can a result of a serendipitous screening campaign with the aim to discover novel chemotypes. The most prevalent type of a hit—weak binders and lead structures with activities in µM range.
Independent of the source, a weak binders always awaits the same fate when it is selected as a lead, namely the interation cycle to improve its potency and selectivity to avoid undesired side effects.

Our solutions accompany your on the long journey of lead optimization and accelerate the whole process. Following this link you will find several perspectives on how our tools are the perfect arsenal to reach our goals.

Typically, the target structure for an active compound is know. Every now and then, it is not.
From cell-based screenings, AI predictions, or animal models, compounds with various biological activities can emerge, including anticancer, antibacterial, and antiparasitic properties. The subsequent identification of the target structure(s) that are engaging with the compound can become a challenge that is not always solved.
In those cases, methods to further improve the compound without the knowledge of the 3D target structure are required.

Discover how to navigate the complexities of ligand-based approaches following this link.

First things first: Smart choice.
Leaving that aside, you are about to create your own in-house compound resource for drug discovery projects. Chemical Spaces are the next generation of ultra-large molecule sets, usually containing billions or even more of entries, that can be used to efficiently mine for relevant chemistry.
Compared to enumerated libraries, Chemical Spaces can be screened faster and will deliver accessible results.

Learn here about the two requirements to set up your own Chemical Space and how to mine from it to accelerate your drug discovery projects.

Diversification in early stages of drug discovery campaigns mitigates the risks of hitting a dead end. Therefore, it is important to find as many diverse chemical scaffolds as possible, in order to have a backup plan if a lead compound proves to be toxic or cannot be further optimized.
In further extent, discovery of new chemical entities (NCEs) covers the concept of scaffold hopping to circumvent patents on a promising molecule and its analogs.

Our methods are proven to deliver chemically diverse structures, tailored for both structure- and ligand-based approaches.
Examples for mining for potential candidates can be found following this link.

Over time, molecule collections start to pile up: One set for project A, two sets for project B, fifteen sets for project C...
Some of these compound sets, or even a comprehensive master set of all in-house compounds, are frequently utilized in virtual screening campaigns to assess whether existing resources might contain promising candidates. In order to profit the most from such legacy collections, a streamlined workflow environment for the whole company is required.

Our solutions support the expansion of your in-house libraries with synthetically accessible compounds, facilitate seamless team and dataset management, and enable the efficient processing of workflows for a streamlined experience.
Read more following this link.

"Compounds, Compounds, everywhere,
Nor any way to prioritize."
If you ask someone why they don’t simply select the top-scoring compounds after a virtual screening, you'll likely be met with a detailed—and often impassioned—explanation. They’ll emphasize that docking scores are far from the only factor to consider, followed by an extensive list of additional criteria essential for effective compound selection.
This entails key interactions, bending of the molecule, clashes, protonation states, chemical diversity, and so on...

For those needing some help in making informed decisions during the compound selection step, we have collected detailed insights on how to be efficient following this link.

Medicinal chemists are experts in designing novel drug candidates to improve a compound's activity or ADME parameters while maintaining key interactions with the target structure. Yet, sometimes even experts need a little help.
In order to support Medicinal Chemists, BioSolveIT has dedicated itself to develop easy-to-operate, graphical software, that provides you with instant feedback on your ideas and helps you ideate on novel ideas how to improve the potency of compounds. From fine-grained modifications to scaffold replacements and compound decorations—the tools help you to think outside the box to master every challenge.

The best part: Our software is very easy to learn and to master. The team can come up with sound ideas and understand assess the quality of results without external help.

Learn how your Medicinal Chemistry Team can unleash their full potential in each drug discovery campaign following this link.

Having access to multiple crystal structures is like owning a personal gold mine, but it comes with a significant bottleneck. This entails the need the comparison of binding sites to identify changes in the tertiary structure, such as side-chain flips, and fast and convenient access to the most interesting analogs of cocomplexed ligands to explore their SARs.

The BioSolveIT environment includes the necessary tools to accelerate the entire compound prioritization process of crystallographic approaches. Learn about 3D assessment, workflow streamlining and rapid SAR exploration following this link.

PROTACs, with their rather unconventional mechanism of action, have been on the rise for years and are receiving increasing attention within the scientific community.
Anyone who has worked with them knows that, to put it mildly, they are not the easiest drugs to design, especially when exploring functionalities beyond the mainstream. Exploring new areas requires access to innovative ideas and valuable resources, enabling efficient discovery of fresh insights and novel modalities.

Our technologies can be implemented to become a game changer for your in-house PROTAC projects. This link covers the topics of discovering novel functionalities for PROTACs, 3D rigidification of linkers, as well as how to expand your libraries with ADME-optimized entities.

The most promising in silico designs are only as valuable as their synthetic accessibility.
We have extensive experience working with companies engaged in AI-driven drug design that benefit from our Chemical Space exploration technology, as well as with pharmaceutical companies leveraging this approach to maximize their in-house resources by integrating it with their computational efforts.

Our tools have been integrated into numerous workflows to facilitate rapid screening of ultra-large molecule libraries for relevant compounds that are either commercially available or can be easily synthesized. Read how BioSolveIT makes your ideas accessible following this link.

Even the most promising drug candidates can encounter roadblocks, including poor cell permeability, toxicity, and rapid metabolism, limiting their therapeutic potential.
All the more frustrating when the target was promising from the start, and the compound itself had the potential to become a blockbuster. To maintain momentum, alternatives are needed—new molecules, ideally similar to what’s already there, just different. The same thing in another color, so to speak.
In the same vein, we shouldn’t forget that the strategy would be the same as when trying to circumvent the limitations around a blockbuster's patent...

To learn how to pull a miracle scaffold out of the hat, click on this link.

In day-to-day work, the accessibility of a building block often determines whether a compound is synthesized. Only in special cases is a building block synthesized in-house. As a result, over the years, an entire arsenal of building blocks accumulates in labs and inventories, which often go untouched. This is a missed opportunity, as these building blocks could hold solutions for many projects—if only they were considered a resource.
Paired with in-house reactions into synthetic strategies, they could yield true gems that explore entirely uncharted areas of chemical space!

Learn following this link how our approaches can get the most out building blocks and expertise.

As a CRO, switching between diverse projects and managing various target classes is your daily business. Each project brings its own requirements and unique challenges, all of which must be aligned. This makes efficiency and flexibility essential, with every part of the team working in sync to deliver reliable results.

Our software is perfectly suited for CROs, as it accelerates workflows, is easy to learn and master, and can be quickly adopted by anyone on the team. Both medicinal and computational chemists can utilize it to rationalize SARs within a compound series and to come up with sound ideas for follow up. Most importantly, it enables you to present your research findings with clarity and sophistication, providing a strong foundation for data-driven discussions and informed decision-making.
Learn more following this link.

Alongside potency and selectivity, ADME parameters are among the most important metrics considered for a drug. Therefore, it makes sense to estimate in advance whether the desired target values can be achieved with a candidate or if they will be missed by a wide margin.

Having a plan B is also essential in case primary strategies fail. For metabolically unstable groups and substructures, bioisosteres should be considered that can maintain the core interactions with the target structure while improving stability.

Find detailed insights following this link.

Covalent drugs are certainly one of the most intriguing topics in modern drug discovery. However, anyone who has ever worked on molecular design in this field knows how cumbersome the software can be to use and how challenging lead optimization can become.

We offer solutions tailored for researchers involved in covalent drug design that enable sophisticated drug design at all target classes and residues of interest.
Furthermore, our Chemical Space exploration technology provides access to the largest hunting ground for drugs containing covalent warheads.
Read more about BioSolveIT's approaches to covalent drug design following this link

Tool compounds are useful molecules that don't need to meet drug-like criteria. They may exhibit moderate to good potency and selectivity, and as long as they effectively serve their purpose to understand and study the target structure, they fulfill their role completely.
The challenges arise when, after confirming target validity, the search for potential drug candidates begins. It is far from trivial to find structures that not only replicate the key molecular features of the tool compound, forming high-quality interactions within the binding site, but also comply with drug-like functional groups.

Fortunately, there are a few techniques that can be applied to successfully advance toward new potential drug candidates. You will find more insights on our page dedicated to transition from a tool compound to drug-like structures here.

Agricultural and medicinal chemistry are not the same thing, there is no doubt about it.
Molecule libraries are typically designed to meet the needs of pharmaceutical companies, containing drug- and lead-like molecules. Although there may be some overlap between pharmaceutical and agricultural chemistry, the recurring molecular motifs observed in approved compounds often exhibit significant differences, reflecting the unique challenges and opportunities presented by each field.

Chemical Spaces represent a unprecedented hunting ground for novel agrochemistry. Coupled with some smart tricks mentioned on this page, you can significantly expand your possibilities to mine for relevant chemistry for your projects.

Enumerated libraries have their limits. To effectively search truly large compound libraries for relevant molecules, innovative approaches are required. Bigger really is better, as it leads to better and more potent molecules.^[1],[2],[3]

Chemical Spaces are combinatorial marvels consisting of building blocks and chemical reactions that define how these can be assembled into compounds. The resulting combinatorial explosion generates very large molecule clusters that, by design, contain synthetically accessible and drug-like molecules.

• Our "Combinatorial vs. Enumerated, Simplified with Burgers" page explains the differences between enumerated libraries and combinatorial Chemical Spaces clearly and accessibly, backing it up with scientific facts.
• You can read more about the several available Chemical Spaces follwing this page.

The various Chemical Space search methods (so-called "Components") are also available as command line tools that can be integrated into your consisting workflows. Computational chemists can use advanced setting for large-scale mining of relevant compounds to fine-tune their results.
Those additional settings include:

• FTrees: expansion of alternative results/alternative synthesis routes
• SpaceLight: selection of different fingerprints (e.g., ECFP, fCSFP, iCSFP, tCSFP and their respective variants)
• SpaceMACS: SMARTS definition

Detailed information can be found in the respective User Guides.

The current demands on a successful computational chemistry infrastructure also encompass the realm of high-performance computing (HPC) to efficiently process large data sets. Accordingly, systems need to be scalable to ensure they remain future-proof.

Beyond the fact that our platforms and components synergistically integrate to cover the drug discovery process from various perspectives, we have also taken into account the aspect of maximizing the use of in-house computational resources to quickly and reliably deliver results.

• HPSee is our scalable screening workflow environment that can be integrated into your in-house workflows to process larger data volumes on your hardware efficiently. It allows the management of databases (e.g., molecule libraries and Chemical Spaces) as well as the orchestration of the team.

A wide range of BioSolveIT applications for structure- and ligand-based drug design is also available as command-line tools for the most common operating systems. These can be easily executed by users with preferred settings and adjusted with specific parameters to achieve the desired results.

• FlexX: Docking algorithm.
• HYDE: De-solvation-aware scoring algorithm.
• FastGrow: Ultra-fast exploration of binding sites for shape-complementary fragments.
• Conformator: Generation of 3D conformations of molecules.
• FlexS: Ligand-based superpositioning and virtual screening.