G1/S-specific cyclin-D2

G1/S-specific cyclin-D2 - Focused Library Design

Available from Reaxense

This protein is integrated into the Receptor.AI ecosystem as a prospective target with high therapeutic potential. We performed a comprehensive characterization of G1/S-specific cyclin-D2 including:

1. LLM-powered literature research

Our custom-tailored LLM extracted and formalized all relevant information about the protein from a large set of structured and unstructured data sources and stored it in the form of a Knowledge Graph. This comprehensive analysis allowed us to gain insight into G1/S-specific cyclin-D2 therapeutic significance, existing small molecule ligands, relevant off-targets, and protein-protein interactions.

Fig. 1. Preliminary target research workflow

2. AI-Driven Conformational Ensemble Generation

Starting from the initial protein structure, we employed advanced AI algorithms to predict alternative functional states of G1/S-specific cyclin-D2, including large-scale conformational changes along "soft" collective coordinates. Through molecular simulations with AI-enhanced sampling and trajectory clustering, we explored the broad conformational space of the protein and identified its representative structures. Utilizing diffusion-based AI models and active learning AutoML, we generated a statistically robust ensemble of equilibrium protein conformations that capture the receptor's full dynamic behavior, providing a robust foundation for accurate structure-based drug design.

Fig. 2. AI-powered molecular dynamics simulations workflow

3. Binding pockets identification and characterization

We employed the AI-based pocket prediction module to discover orthosteric, allosteric, hidden, and cryptic binding pockets on the protein’s surface. Our technique integrates the LLM-driven literature search and structure-aware ensemble-based pocket detection algorithm that utilizes previously established protein dynamics. Tentative pockets are then subject to AI scoring and ranking with simultaneous detection of false positives. In the final step, the AI model assesses the druggability of each pocket enabling a comprehensive selection of the most promising pockets for further targeting.

Fig. 3. AI-based binding pocket detection workflow

4. AI-Powered Virtual Screening

Our ecosystem is equipped to perform AI-driven virtual screening on G1/S-specific cyclin-D2. With access to a vast chemical space and cutting-edge AI docking algorithms, we can rapidly and reliably predict the most promising, novel, diverse, potent, and safe small molecule ligands of G1/S-specific cyclin-D2. This approach allows us to achieve an excellent hit rate and to identify compounds ready for advanced lead discovery and optimization.

Fig. 4. The screening workflow of Receptor.AI

Receptor.AI, in partnership with Reaxense, developed a next-generation technology for on-demand focused library design to enable extensive target exploration.

The focused library for G1/S-specific cyclin-D2 includes a list of the most effective modulators, each annotated with 38 ADME-Tox and 32 physicochemical and drug-likeness parameters. Furthermore, each compound is shown with its optimal docking poses, affinity scores, and activity scores, offering a detailed summary.

G1/S-specific cyclin-D2

partner:

Reaxense

upacc:

P30279

UPID:

CCND2_HUMAN

Alternative names:

Alternative UPACC:

P30279; A8K531; Q13955; Q5U035

Background:

G1/S-specific cyclin-D2 plays a pivotal role in cell cycle regulation, particularly during the G1/S transition. It forms a complex with CDK4, leading to the phosphorylation and inhibition of the retinoblastoma protein family, thus facilitating cell cycle progression. This protein's activity is a critical integrator of mitogenic and antimitogenic signals.

Therapeutic significance:

G1/S-specific cyclin-D2 is implicated in Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3, a condition characterized by brain and digit abnormalities. Targeting the cyclin D2-CDK4 complex pathway offers a promising therapeutic strategy for managing this syndrome and potentially other cell cycle-related disorders.