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 Serpin H1 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 Serpin H1 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 Serpin H1, 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 Serpin H1. 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 Serpin H1. 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 Serpin H1 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.
Serpin H1
partner:
Reaxense
upacc:
P50454
UPID:
SERPH_HUMAN
Alternative names:
47 kDa heat shock protein; Arsenic-transactivated protein 3; Cell proliferation-inducing gene 14 protein; Collagen-binding protein; Rheumatoid arthritis-related antigen RA-A47
Alternative UPACC:
P50454; B3KVJ3; P29043; Q5XPB4; Q6NSJ6; Q8IY96; Q9NP88
Background:
Serpin H1, also known as the 47 kDa heat shock protein, plays a crucial role in the human body by specifically binding to collagen. This protein, with alternative names such as Arsenic-transactivated protein 3 and Collagen-binding protein, functions as a chaperone in the biosynthetic pathway of collagen, indicating its pivotal role in maintaining the structural integrity of various tissues.
Therapeutic significance:
Given its involvement in Osteogenesis imperfecta 10, a disorder characterized by bone fragility and susceptibility to fractures, understanding the role of Serpin H1 could open doors to potential therapeutic strategies. This protein's function in collagen binding and processing underscores its potential as a target for developing treatments aimed at enhancing bone strength and resilience.
