PROTAC, also known as PROteolysis-Targeting Chimera, is a heterodimeric bifunctional small molecule compound that induces targeted protein degradation via the ubiquitin-proteasome system. Using state-of-the-art computational biology and cheminformatics, CD ComputaBio aims to facilitate the rational design, optimization and evaluation of PROTAC molecules.
Overview of PROTAC and Its Analysis
PROTACs are heterobifunctional molecules consisting of a target-binding warhead, a linker, and an E3 ligase recruiter, enabling selective degradation of disease-causing proteins. Unlike traditional inhibitors, PROTACs operate catalytically, offering advantages such as targeting undruggable proteins, overcoming resistance, and achieving prolonged pharmacodynamic effects. Researchers have now developed thousands of PROTAC molecules, and many are in clinical development.
Fig. 1 Overview steps of entire target protein degradation by PROTACs. (Gao H, et al., 2020)
PROTAC analysis refers to the systematic evaluation and optimization of PROTAC molecules. Our multidisciplinary analytical framework combines computational, biochemical, and structural techniques to address the unique challenges of PROTAC design, including ternary complex formation, pharmacokinetics, and target specificity. The core objectives of PROTAC analysis are as follows:
Target Degradation Efficiency
Quantify the ability of PROTACs to induce ubiquitination and proteasomal degradation of the protein of interest (POI).
01
Ternary Complex Stability
Evaluate the formation and durability of the POI-PROTAC-E3 ligase ternary complex.
02
Selectivity Profiling
Minimize off-target degradation by assessing interactions with non-target proteins.
03
Pharmacokinetic Optimization
Improve cellular permeability, metabolic stability, and tissue distribution.
04
Our Services
By multi-scale modeling, AI-driven algorithms, and high-performance computing, CD ComputaBio's PROTAC analysis service covers molecular dynamics, binding kinetics, bioavailability & toxicity evaluation to accelerate PROTAC optimization. Our flexible platform also accommodates ternary complex analysis, linker design, and other customized development needs.
PROTAC Molecular Dynamics Service
We use advanced molecular dynamics simulations to analyze ternary complex stability, linker flexibility, and binding interactions. High-performance computing enables the prediction of optimal PROTAC conformations for enhanced degradation efficiency.
PROTAC Binding Kinetics Analysis Service
Computational kinetic modeling evaluates PROTAC-target-E3 ligase binding rates and residence times to optimize degradation kinetics. Markov state models and simulations help identify high-affinity PROTACs with prolonged target engagement.
PROTAC Bioavailability Prediction Service
Machine learning and PBPK modeling predict PROTAC solubility, permeability, and metabolic stability for improved drug-like properties. The service aids in selecting candidates with optimal ADME profiles for in vivo applications.
PROTAC Toxicity Prediction Service
Deep learning algorithms screen for off-target degradation risks and potential organ-specific toxicities. Structural alert analysis minimizes adverse effects by flagging reactive metabolites and immunogenicity concerns early in development.
Our Technical Advantages
- Multi-Scale Modeling: Integrates quantum mechanics, molecular mechanics, and coarse-grained simulations for comprehensive PROTAC analysis.
- High-Performance Computing: Utilizes GPU-accelerated algorithms for rapid large-scale PROTAC screening and optimization.
- ML-Driven Predictions: Employs deep neural networks for ADMET profiling and ternary complex stability assessment.
- Validated Workflows: Combines in silico predictions with wet-lab collaborations to ensure translational relevance.
CD ComputaBio's PROTAC analysis service provides end-to-end solutions for the design and evaluation of PROTAC-based therapeutics. By combining advanced molecular modeling, kinetic analysis, and machine learning, the service accelerates the development of selective and efficacious protein degraders. For detailed inquiries or collaboration opportunities, contact us for tailored computational support.
Reference:
- Gao H.; et al. ROTAC technology: opportunities and challenges[J]. ACS medicinal chemistry letters. 2020, 11(3): 237-240.
* For Research Use Only.
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