Analysis and visualization of the diversity of chemical space is becoming increasingly important, especially for the characterization and design of compound libraries used for hit discovery in HTS campaigns. Compound shape has long been recognized as an essential factor in molecular recognition between ligands and their biological targets. Moreover, the optimal spatial orientation of the pharmacophoric features is crucial for the efficient binding of ligand small molecules.
Aiming to construct a high quality 3D-shaped Diversity Compound Library, BOC Sciences has established a set of criteria that allow the assessment of 3D diversity of molecules using the plane of best fit and principal moment of inertia, which are currently the best indicators for describing the shape of molecule.
Application of 3D-shaped Diversity Compound Library
- Discover protein-protein interaction inhibitors that often involve scaffolds containing 3D features
- Provide compounds containing conformations with distinct 3D shapes which can be captured at corresponding protein binding sites via X-ray crystallography method
- Molecules containing significant 3D shapes often exhibit ideal aqueous solubility
Figure 1. The three-dimensionality profile of the drug-like chemistry space. (a) The PMI ternary density plot and (b) the PBF box-and-whisker plot. (Meyers, J.; et al. 2016)
Plane of Best Fit (PBF)
BOC Sciences has employed an advanced computational method called PBF to quantify and characterize the 3D character of molecules. PBF is introduced across all the heavy atoms of the molecule in a given conformation. The average distance of all heavy atoms from the PBF describes the distance of the molecule from the 2D shape, thus providing a quantitative description of the 3D shape. We therefore use this strategy to rapidly analyze a large number of compounds and apply it to different datasets containing fragment-like, drug-like and natural product compound, generating our 3D-shaped Diversity Compound Library.
Principal Moment of Inertia (PMI)
The Principal Moment of Inertia descriptor is another recently published and widely adopted molecular descriptor to characterize the three-dimensionality of molecular structures, which provides a useful and rapid method for assessing the degree to which a given molecular geometry is rod-shaped, disc-shaped, and spherical. BOC Sciences utilizes PMI method to calculate and evaluate the 3D character of molecules and their substructures.
Table1. Physicochemical parameters for the BOC Sciences 3D-shaped Diversity Compound Library
| Parameter | Value |
| MW | 250-500 |
| ClogP | <10 |
| Number of Rotatable Bonds | ≤10 |
| Number of H Donors | ≤5 |
| Number of H Acceptors | ≤10 |
| TPSA | ≤140 |
| Number of Rings | >1 |
| Compounds with ‘undesirable’ functionalities | Removed |
| Fsp3 | ≥0.35 |
| Molecular Flexibility | ≥0.35 |
| Molecular Complexity | ≥0.35 |
| npr1 | ≥0.15 |
| npr2 | ≥0.85 |
Features of General Fragments Library
- Our chemical space can be further expanded through our in-house developed and validated synthetic procedures
- BOC Sciences can provide customized 3D-shaped Diversity Compound Library design services based on your requirements
What We Deliver
- Delivered within 2 weeks in any customer-preferred format
- Powders, dry films or DMSO solutions formatted in vials, 96 or 384-well plates
- All compounds have a minimum purity of 90% assessed by 1H NMR
- Analytical data is provided
BOC Sciences provides professional, rapid and high-quality services of 3D-shaped Diversity Compound Library design at competitive prices for global customers. Personalized and customized services of 3D-shaped Diversity Compound Library design can satisfy any innovative scientific study demands. Our clients have direct access to our staff and prompt feedback to their inquiries. If you are interested in our services, please contact us immediately!
Reference
- Meyers, J.; et al. On the origins of three-dimensionality in drug-like molecules. Future medicinal chemistry. 2016. 8(14): 1753-1767.
