PROTAC Molecular Dynamics Service
PROTAC molecular dynamics is a computational approach that simulates the dynamic interactions between PROTAC molecules, target proteins, and E3 ubiquitin ligases to predict degradation efficiency. CD ComputaBio offers a cutting-edge PROTAC Molecular Dynamics Service that leverages computational modeling to accelerate drug discovery and development processes.
Introduction to PROTAC Molecular Dynamics
Molecular dynamics (MD) simulation is the foundation of traditional small molecule drug (TSMD) development. Rigorous MD simulations help scientists overcome the limitations of static modeling techniques by capturing conformational changes over time, solvent effects, and binding/debinding events, thereby deepening the understanding of degradation mechanisms. Given the similarities between TSMD and PROTAC, scientists have begun to extend MD to PROTAC designs.
Fig. 1 Mode of action of PROTACs. (Sun X, et al., 2019)
The unique pharmacology of PROTAC, coupled with its large average size and lack of public training data, makes MD a particularly important tool in PROTAC drug development. Key benefits of PROTAC molecular dynamics include the ability to predict optimal linkage lengths, evaluate warhead binding modes, and assess the stability of ternary complexes under physiological conditions.
Our Services
CD ComputaBio's PROTAC molecular dynamics service is dedicated to elucidating the complex mechanisms of action of PROTACs, based on multidisciplinary expertise in biology, chemistry, computer science, and pharmacology, as well as state-of-the-art computational tools. Our services include but are not limited to the following:
All-Atom Molecular Dynamics (MD)
Simulation Service
Deploying a hybrid AMBER/CHARMM force field for PROTAC-target-E3 ternary systems. Our µs-level simulations capture warhead binding kinetics and allosteric propagation, enhanced by GPU-accelerated accelerated molecular dynamics protocols for linker conformation optimization.
Steered Molecular Dynamics (SMD)
Service
CD ComputaBio applies SMD with CHARMM36m to simulate PROTAC dissociation under physiological forces. We map molecular glue vs. classical PROTAC unbinding paths and validate Fc-domain dynamics with cryo-EM density-guided constraints.
Umbrella Sampling Simulation
Service
Quantifying PROTAC-induced binding thermodynamics using dual reaction coordinates (E3/target distance + linker torsion). Our PMF analysis predicts ternary complex stability and optimizes PEG linker entropy through WHAM-validated free energy landscapes.
Targeted Molecular Dynamics (TMD)
Service
Guiding PROTAC systems to ubiquitination-ready states via progressive RMSD constraints. Our TMD protocols reconstruct ARV-110's clinical conformation shifts and quantify phosphorylation site activation barriers with <15% CV deviation.
Replica Exchange Molecular Dynamics
(REMD) Services
Our temperature-scaled REMD resolves PROTAC linker flexibility across 32 replicas. We predict membrane permeability and solvent-shell reorganization using adaptive Hamiltonian sampling, achieving 95% convergence in 200 ns/replica.
More Customized Simulation
Services
Exploring the extended computational toolbox for PROTAC challenges. Leverage the proprietary algorithm library to address your specific ternary system requirements, with guaranteed ≥ 90% technical compatibility across all service modules.
PROTAC Simulation Strategy Portfolio
With extensive PROTAC expertise and proven project success, we deliver the following validated multi-scale strategies.
- Core Protocol: All-Atom MD + Umbrella Sampling (Addresses 80% routine requirements)
- Mechanism Elucidation: All-Atom MD + REMD + TMD (Full conformational transition pathway mapping)
- Degradation Efficiency Optimization: SMD + QM/MM (Linker bond stability profiling)
- Preclinical Validation: All-Atom MD + Alchemical FEP (Binding energy prediction error <1 kcal/mol)
The Process of PROTAC Molecular Dynamics Service
Project Initiation
Our Service starts with a thorough consultation with our clients to understand their specific research goals and requirements.
1
Computational Modeling
We perform molecular docking to predict the binding mode of PROTACs to target proteins and assess the energetics of their interactions.
2
Molecular Dynamics Simulations
We conduct molecular dynamics simulations to study the structural dynamics and flexibility of PROTAC-protein complexes in solution.
3
Data Analysis and Interpretation
We provide detailed reports and visualizations to guide our clients in the design and optimization of PROTACs.
4
Advantages of Our Services
Expertise and Experience
With a team of seasoned computational biologists and drug discovery experts, CD ComputaBio brings a wealth of experience and knowledge to PROTAC molecular dynamics services, ensuring high-quality results and actionable insights.
State-of-the-Art Infrastructure
Our company is equipped with cutting-edge computational resources, software tools, and algorithms for conducting complex molecular dynamics simulations with precision and efficiency, enabling comprehensive analyses of PROTAC behavior.
Customized Solutions
CD ComputaBio offers tailored solutions to meet the unique requirements of each client, providing personalized approaches to PROTAC design, optimization, and characterization based on specific project objectives and constraints.
CD ComputaBio stands as a trusted partner in the realm of PROTAC molecular dynamics services, offering unparalleled expertise, innovative approaches, and customized solutions for accelerating drug discovery workflows. For detailed inquiries or collaboration opportunities, contact us for tailored computational support.
Reference:
- Sun X., et al. PROTACs: great opportunities for academia and industry[J]. Signal transduction and targeted therapy. 2019, 4(1): 64.
* For Research Use Only.
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