Virtual screening libraries have been widely used as useful tools for the discovery of substrates, inhibitors, etc. Scientists therefore can obtain new compounds by establishing virtual combinatorial libraries. The virtual screening library allows the selection of the best binding constituent from all candidate molecules, thus accelerating the chance of identifying lead compounds for drug discovery. The virtual screening library design integrates all methods developed for virtual screening of existing compound libraries, including similarity-based compound clustering techniques and structure-based docking and scoring.
BOC Sciences has integrated the library generation process/design and the evaluation process/scoring to design the virtual libraries. Moreover, we apply the predictions and the degrees of structural freedom defined by chemistry.
Figure 1. A schematic of the Gypsum-DL algorithm for generating ring-conformational forms. (Ropp, P. J.; et al. 2019)
Our Strategie
BOC Sciences mainly employs ligand structure-, protein structure- and interaction-based method to construct our virtual libraries:
Ligand structure-based design
We use a ligand structure-based approach to synthesize virtual screening libraries when structural information about the target is not available. Our ligand-based library design starts with the calculation of descriptors to characterize the structure of the target molecule, followed by quantitative structure-activity relationships (QSAR) to optimize and obtain the desired library features.
Protein structure-based design
BOC Sciences uses a rapid docking and scoring procedure to filter the virtual ligand list. The docking method is utilized to find a match between each ligand and a set of site points, and then a scoring function is applied to estimate the binding energy. In addition, our experts can increase the enrichment factors employing a novel ‘hybrid’ scoring function by combining docking with pharmacokinetic constraints and knowledge-based method to obtain better predictions of binding modes.
Interaction-based design
We combine ligand and protein-based design with experimental protein-ligand data to perform the interaction-based design.
Figure 2. A virtual small-molecule library by desalting the input compounds and considering alternate ionization, tautomeric, chiral, and cis/trans isomeric states. (Ropp, P. J.; et al. 2019)
Our Services
Molecules constructed based on the in silico reactions can be easily synthesized. BOC Sciences has developed validated, high-quality in silico modeling techniques to generate a large library of composite model combinations to support virtual screening.
BOC Sciences has many years of synthetic experience, enabling to deliver top-quality conformational models, rigid structures and torsional angle structures with reliable energy. In addition, we support rapid and automated 3D conformation design techniques to generate 3D structures of small molecules for high-throughput virtual screening.
BOC Sciences' exclusive interface enables diverse library enumeration for fast and efficient virtual chemical library design. Our team can easily create synthetic virtual compound libraries in just a few steps using template-, scaffold-, and reaction-based enumeration techniques.
The aim of de novo molecular design is to generate new active molecules during the drug development process. The advantage over other molecular design techniques is that only a relatively small number of molecules need to be synthesized and the chemical space can be explored through search or optimization procedures. BOC Sciences applies various machine learning (ML) and deep learning techniques for de novo molecular design to assist in virtual library construction.
BOC Sciences provides professional, rapid and high-quality services of Virtual Screening Library design at competitive prices for global customers. Personalized and customized services of Virtual Screening 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
- Ropp, P. J.; et al. Gypsum-DL: an open-source program for preparing small-molecule libraries for structure-based virtual screening. Journal of Cheminformatics. 2019. 11(1): 34-46.
