Chemical Space Docking

In recent years, there has been an explosive growth in the purchaseable compound library that can be used for virtual screening and analysis. The current screening library is larger and more diverse, which can be applied to identify more effective hit compounds and open up a new chemical space represented by a new core scaffold. Therefore, the cost of computer screening methods, in which every molecule in the library must be enumerated and evaluated independently, is getting higher and higher. Scientists adopt docking technology developed based on compound space has significantly improved the throughput of traditional docking methods. Chemical space docking is a novel approach for virtual screening which allows for handling multiple molecules occurring in combinatorial chemical spaces. Chemical space docking aims to predict actives based on their binding mode after a docking procedure with subsequent scoring of the complexes. Yet the source of the docked molecules is no longer an enumerated library but a combinatorial built-up 'space' of zillions of molecules.

Figure 1. Docking studies of pteroyl-tyrosinate. Chemical structures of (a) folic acid (FA) and (b) pteroyl-tyrosinate. (c) Molecular dynamics prediction of the superimposition of folic acid (orange) with pteroyl-tyrosinate (gray) and (d) binding interaction of pteroyl-tyrosinate in the activesite of the FRα (PDB code: 4LRH). The binding pocket of FRα in space-filling mode (e) side and (f) top view with pteroyl-tyrosinate in stick mode. (Mahalingam, S. M.; et al. 2018)

Modeling Process

1. Building block docking

• We use only a small fraction which is also called the building blocks to create the space.
• We then perform an energetic assessment of the binding mode in which the growing of small molecules is conducted. Binding modes of interesting candidates are investigated for extension possibilities at molecular functionalities. And those molecules with potential to be evolved into good binders enter the next step.

2. Combinatorial compound generation

Our experts have professional knowledge on what functional groups of a molecule are able to combine with those of other building blocks, and we create and dock them again into the target.

3. Results delivery

We provide a set of molecules that are likely to bind to the target of interest after the redocking of generated compounds using our binding mode assessment & filtering.

Features of Our Chemical Space Docking

• Recover more than 80% of the experimentally confirmed hits
• Preserve the diversity of the experimentally confirmed hit compounds
• Low cost for computation

Our Modeling Services

• Alfa Chemistry introduces a protocol for machine learning-enhanced docking based on active learning.
• We can identify the best scoring compounds and explore a large region of chemical space.
• Our chemical space docking is able to capture almost all the high scoring scaffolds in the library found by exhaustive docking together with automated redocking of the top compounds.

Alfa Chemistry's Advantages

• Our method allows the exploration of the whole chemical space with a minuscule of the computational efforts required otherwise.
• Our robust chemical reactions and in-house knowledge are useful in creating the chemical space.

Our chemical space docking services remarkably reduce the cost, promote further experiments, and accelerate the process of drug design for customers worldwide. Our personalized and all-around services will satisfy your innovative study demands. If you are interested in our services, please don't hesitate to contact us. We are glad to cooperate with you and witness your success!

Reference

• Mahalingam, S. M.; et al. Evaluation of Novel Tumor-Targeted Near-Infrared Probe for Fluorescence-Guided Surgery of Cancer. Journal of Medicinal Chemistry. 2018, 61: 9637-9646.