Flexible Gaussian Accelerated Molecular Dynamics to Enhance Biological Sampling

Area of Science:

• Computational chemistry
• Molecular dynamics simulations
• Biophysics

Background:

• Molecular dynamics (MD) simulations face challenges in achieving adequate sampling for complex molecular events due to high energy barriers.
• Enhanced sampling techniques, including Gaussian accelerated molecular dynamics (GaMD), have been developed to overcome these limitations.
• GaMD employs a biasing potential to modify the energy landscape, reducing barrier heights and improving sampling without prior system knowledge.

Purpose of the Study:

• To introduce a flexible selective Gaussian accelerated molecular dynamics (GaMD) approach implemented in GROMOS.
• To enable users to define multiple boosting potentials across various regions of interest.
• To demonstrate the advantages and applicability of this flexible selective GaMD method for studying molecular conformational changes.

Main Methods:

• Implementation of a fully flexible selective GaMD approach within the GROMOS simulation package.
• Application of multiple, user-defined boosting potentials to specific regions of molecular systems.
• Validation using established test systems (alanine dipeptide, chignolin peptide) and extension to glycans and glycosylated proteins.

Main Results:

• The flexible selective GaMD approach successfully enhances sampling by effectively lowering energy barriers in user-defined regions.
• Demonstrated advantages over previous selective GaMD methods in terms of flexibility and applicability.
• Successfully applied to study conformational dynamics in glycans and glycosylated proteins, showcasing broader utility.

Conclusions:

• The developed flexible selective GaMD method provides a powerful and versatile tool for enhanced molecular simulations.
• This approach significantly improves the ability to study complex molecular events, including those involving glycans and glycosylated proteins.
• Offers a straightforward way to customize enhanced sampling strategies for diverse molecular systems.