From quantum to subcellular scales: multi-scale simulation approaches and the SIRAH force field

Area of Science:

• Molecular and Cellular Biology
• Computational Biology
• Biophysics

Background:

• Advanced structural biology techniques offer high-resolution insights, down to the whole cell level.
• Computational methods are crucial for understanding molecular processes across diverse temporal and spatial scales.
• Integrating different scales is essential for addressing complex biological questions.

Purpose of the Study:

• To provide an overview of computational methods bridging classical and coarse-grained resolutions.
• To emphasize the SIRAH force field for coarse-grained and multi-scale simulations.
• To demonstrate a multi-scale simulation scheme combining quantum mechanics with DNA models.

Main Methods:

• Overview of computational methods for multi-scale simulations.
• Focus on the SIRAH force field for coarse-grained modeling.
• Implementation of a multi-scale simulation integrating quantum calculations with classical/coarse-grained DNA representations.

Main Results:

• The SIRAH force field is highlighted for its utility in coarse-grained and multi-scale simulations.
• A proof-of-concept multi-scale simulation scheme was successfully implemented for double-stranded DNA.
• This approach enables the study of large conformational fluctuations and their impact on DNA base pair reactivity.

Conclusions:

• Multi-scale simulation frameworks are powerful tools for modern molecular and cellular biology.
• The developed scheme allows for the integration of quantum effects within large-scale conformational dynamics.
• This opens new avenues for investigating how chromatin dynamics influence molecular reactivity.