Quantum Mechanics/Molecular Mechanics (QM/MM) Simulation Service
Unveil Glycobiology Through Quantum Mechanics/Molecular Mechanics (QM/MM) Simulation
At CD BioGlyco, our research team employs a hybrid computational model for comprehensive analysis of Glycan-Molecular Interactions. We integrate the accuracy of QM calculations with the efficiency of MM potentials, allowing for the prediction and analysis of the dynamic nature of glycan-molecular interactions. Our service reduces the complex computational process of full-system QM calculations by concentrating on the most crucial interaction areas. This ensures accurate and detailed simulations of the electronic structure and dynamics in glycan-molecular interactions.
Our QM/MM methods partition the entire system into distinct localized regions, each treated at different levels of theory. In investigations of enzymatic reactions, the QM region typically encompasses the active site, where chemical reactions occur, along with pertinent amino acid residues in proximity. Here, QM methods are applied. Meanwhile, the surrounding MM region is handled at the MM level, exerting influence on the QM region through electrostatic and steric interactions. The QM/MM methods not only offer energy calculations for a specific structure but also integrate seamlessly with various techniques for exploring the extensive configuration space of large biomolecules. These include:
- Optimization
- Molecular dynamics (MD)
- Metadynamics
- Monte Carlo methods
Through these integrations, our researcher improves the precision of evaluations in intricate systems, specifically in glycan-related enzymatic reactions occurring in detailed solvent surroundings. Our service is suitable for analyzing carbohydrate-active enzymes involved in biochemical reactions such as glycosylation, as well as the synthesis and hydrolysis of carbohydrates, lectins, antibodies, sugar transporters, glycosaminoglycans, and lipopolysaccharides.
Publication Data
Technology: Substrate conformational dynamics, QM/MM, Molecular dynamics
Journal: Journal of Chemical Information and Modeling
Published: 2022
IF: 5.6
Results: Through extensive conventional and QM/MM molecular dynamics simulations on human pancreatic α-amylase, this study delves into the intricate details of enzyme catalysis. The authors found that the enzyme's rigid backbone dynamics and its close interaction with the buried part of the substrate are crucial for catalytic processes. By analyzing catalytic distances and substrate conformations, the study provides insights into the glycosylation step, shedding light on the kinetics and thermodynamics involved. Notably, the role of key residues and water molecules in promoting enzyme catalysis was explored, and ultimately authors proposed a novel approach to identify reactive conformations in enzyme-substrate complexes. The discoveries not only enhance our comprehension of enzyme dynamics but also provide important insights for the design of drugs and the engineering of enzymes.
Fig.1 Left: Schematic representation of the glycosylation mechanism of α-amylase with the main distances highlighted in blue. Right: Representation of a minimal active site of α-amylase and the distances analyzed in this study. (Neves, et al., 2022)
Advantages
- This hybrid approach allows us to overcome the computational limitations of full QM methods, providing detailed insights into glycan-molecular interactions.
- Our QM/MM simulation service leverages the strengths of both QM and MM methods, enabling comprehensive analyses that capture the intricate interplay between glycan structures and molecular environments.
- Our research team integrates advanced computational techniques to study complex glycan-related biological processes.
Applications
- Our service can be used for conducting dynamics simulations of carbohydrates by integrating QM/MM methods to explore interactions between structure and function.
- Our service is useful for evaluating interactions between potential carbohydrate-related drug molecules and target molecules through QM/MM simulations to guide drug design and screening processes.
- Our service can be applied to designing novel glycosylation inhibitors to optimize performance.
Frequently Asked Questions
- What other methods are there for analyzing carbohydrate-molecular interactions?
- Force field
- Free-energy calculation
- Metadynamics calculations
- Molecular robotics
- Docking calculation
- DFT-based ab initio simulation
- Semiempirical method
- Molecular dynamics simulation
- Heuristic method (Monte Carlo and genetic algorithms)
- Coarse-grained method
- What are the types of QM/MM methods?
- In QM/MM methods, two main approaches exist for coupling QM and MM components: additive and subtractive methods. Additive methods sum the energies of QM and MM regions with a coupling term, widely used in biomolecular simulations. However, accurately calculating this coupling term, especially with link atoms or electrostatic perturbations in the QM Hamiltonian, poses challenges. Conversely, subtractive methods independently compute different parts with varied theory levels, combining their energies to yield a final corrected system energy. This approach allows straightforward application of standard QM and MM methods, minimizing modifications in QM/MM implementations.
CD BioGlyco helps clients explore the catalytic mechanism of glycosyltransferases with a QM/MM approach. Our modeling process encompasses three key stages, constructing a structural model, developing a QM/MM model, and simulating an enzymatic reaction. In general, glycan-molecular interaction is of fundamental interest in glycobiology, contact us to obtain more information about our glycoinformatics service.
Reference
- Neves, R.; et al. Role of enzyme and active site conformational dynamics in the catalysis by α-amylase explored with QM/MM molecular dynamics. Journal of Chemical Information and Modeling. 2022, 62(15): 3638-3650.
For research use only. Not intended for any diagnostic use.
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