AI-ACCELERATED DRUG DISCOVERY
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 BLOC-3 complex member HPS1 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 BLOC-3 complex member HPS1 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 BLOC-3 complex member HPS1, 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 BLOC-3 complex member HPS1. 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 BLOC-3 complex member HPS1. 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 BLOC-3 complex member HPS1 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.
BLOC-3 complex member HPS1
partner:
Reaxense
upacc:
Q92902
UPID:
HPS1_HUMAN
Alternative names:
Hermansky-Pudlak syndrome 1 protein
Alternative UPACC:
Q92902; A8MRT2; O15402; O15502; Q5TAA3; Q8WXE5
Background:
The BLOC-3 complex member HPS1, also known as Hermansky-Pudlak syndrome 1 protein, plays a pivotal role in cellular processes. It functions as a guanine exchange factor for RAB32 and RAB38, facilitating the conversion of these molecules from an inactive GDP-bound form to an active GTP-bound form. This activity is crucial for melanin production and melanosome biogenesis, highlighting the protein's significant role in pigmentation.
Therapeutic significance:
HPS1's involvement in Hermansky-Pudlak syndrome 1, a disorder characterized by oculocutaneous albinism, bleeding issues, and lysosomal storage defects, underscores its therapeutic potential. Targeting HPS1 could lead to innovative treatments for this syndrome, particularly in managing pulmonary fibrosis, a major cause of mortality in affected individuals.
