Umbrella Sampling Simulation Service
Umbrella sampling simulation, a powerful enhanced sampling method, is essential in computational biology and drug development. By dividing the reaction coordinate, it overcomes sampling limitations caused by high energy barriers in molecular dynamics (MD) simulations. This enables accurate calculation of the potential of mean force (PMF), revealing biomolecular dynamics and interaction mechanisms. CD ComputaBio's technology platform provides comprehensive solutions for complex scenarios like drug-membrane permeation and enzyme catalysis, integrating adaptive umbrella sampling, machine learning potential function, and multi-scale modeling (QM/MM + coarse-grained dynamics).
Introduction to Umbrella Sampling Simulation
- 1970s-1990s: Foundation
Torrie and Valleau introduced umbrella sampling, employing harmonic bias potentials to overcome sampling limitations in molecular dynamics (MD) due to high energy barriers.
- 2000s-2010s: Optimization
- 2005: Adaptive methods, such as combining metadynamics with umbrella sampling, emerged to dynamically refine bias potentials and accelerate convergence.
- 2011: Umbrella sampling was combined with QM/MM methods, enabling accurate energy barrier calculations for enzyme-catalyzed reactions.
- 2010s-2020s: Intelligent Integration
- 2019: Pérez de Alba Ortíz et al. developed Adaptive Path CV, integrating metadynamics, guided MD, and umbrella sampling for automated transition path and free energy profile determination.
- 2023: Repository-Based Adaptive Umbrella Sampling (RBAUS) was introduced to seamlessly bridge non-equilibrium and quasi-equilibrium simulations through real-time updates of sampling libraries and bias potentials.
Applications of Umbrella Sampling Simulation
Umbrella sampling's ability to accurately reconstruct free energy landscapes (PMFs) makes it a pivotal tool for analyzing molecular dynamic mechanisms. Its key advantage is overcoming sampling limitations from high energy barriers, revealing 'rare events' inaccessible to traditional molecular dynamics (MD). Thus, umbrella sampling is widely applied in biomedicine, materials science, environmental chemistry, and other fields.
Fig 1. Investigation of Molecular Details of Keap1-Nrf2 Inhibitors Using Molecular Dynamics and Umbrella Sampling Techniques. (Londhe A M, et al., 2019)
Chemical Reaction Mechanisms
Umbrella sampling is used in molecular simulations to calculate free energy profiles for chemical reactions and other molecular processes. It helps overcome the challenge of sampling rarely occurring states that are typically not well-represented in simple molecular dynamics (MD) simulations due to energy barriers.
Materials Science
Umbrella sampling is a highly instrumental method in materials science essential for analyzing intricate processes and understanding the underlying mechanisms behind material behavior. This method enables researchers to meticulously design materials with specific and desired properties.
Drug-Target Binding Kinetics
Umbrella sampling is a computational method used to study drug-target binding kinetics by providing detailed insights into the free energy landscape of binding and unbinding processes. It allows researchers to understand the energetics and dynamics of drug interactions.
Our Services
CD ComputaBio's interdisciplinary team, composed of computational biologists, quantum chemists, and data scientists, has successfully executed many industrial-scale projects. By harnessing sophisticated algorithms, extensive computational resources, and specialized industry expertise, CD ComputaBio excels in umbrella sampling technology, delivering end-to-end support from research inception to industrial deployment for clients worldwide.
By Simulation Types
Long-term Umbrella Sampling Simulations
CD ComputaBio's long- term umbrella sampling simulations are designed for the study of complex systems involving high energy barrier crossings, multi-stable state conversions, and multi-dimensional cooperative motions. This simulation is particularly valuable for investigating global conformational changes in biomacromolecules and the intricate cooperative mechanisms underlying enzyme catalysis.
Short-term Umbrella Sampling Simulations
CD ComputaBio provides short-range umbrella sampling simulations to meet customer needs. Its service can be applied to the study of drug dissociation, ion migration in solution and local structural changes of proteins. This type of system has few degrees of freedom and a single reaction coordinate, which is suitable for rapid sampling.
By Molecular Types
Force Fields in Umbrella Sampling Simulation
CHARMM Force Field
CD ComputaBio's implementation of the CHARMM force field enables accurate and reliable simulations of biomolecular systems, capturing intricate details of molecular interactions and dynamics. By incorporating CHARMM parameters, CD ComputaBio enhances the predictive power of our simulations and refine the structural modeling of proteins.
AMBER Force Field
The AMBER force field, renowned for its versatility and robustness, underpins molecular dynamics simulations with high-fidelity energy calculations and force evaluations. By utilizing AMBER parameters, CD ComputaBio ensures the accuracy and consistency of our simulations, enabling comprehensive analyses of protein-ligand interactions.
GROMACS Force Field
CD ComputaBio has facilitated efficient simulations of biomolecular systems using the GROMACS force field to explore complex molecular dynamics. By leveraging the GROMACS algorithm, CD ComputaBio has accelerated simulations and enhanced our understanding of protein behavior in different cellular environments.
Our Advantages
- State-of-the-Art Technology
CD ComputaBio employs state-of-the-art computational resources, including high-performance computing clusters that allow for fast, efficient umbrella sampling simulations. Its infrastructure enables us to handle complex simulations while maintaining a quick turnaround time for results.
- Tailored Solutions
CD ComputaBio understands that every research project is unique. Its approach to umbrella sampling simulations is highly customized, allowing it to tailor its services based on specific research goals and requirements.
- Collaborative Approach
CD ComputaBio prioritizes a collaborative atmosphere, maintaining open communication throughout the project. Its clients can expect continuous updates and opportunities for feedback, ensuring alignment with research objectives at every step.
CD ComputaBio provides advanced umbrella sampling simulation services, specifically designed to help researchers solve the most challenging scientific questions. With a commitment to excellence, our expertise, advanced technological resources, and collaborative approach ensure that our clients receive unparalleled support throughout their research journey. Contact us today to learn more about how our services can empower your research.
Reference:
- Londhe A M, Gadhe C G, Lim S M, et al. Investigation of molecular details of Keap1-Nrf2 inhibitors using molecular dynamics and umbrella sampling techniques[J]. Molecules, 2019, 24(22): 4085.
* For Research Use Only.
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