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GLOW: A Workflow Integrating Gaussian-Accelerated Molecular Dynamics and Deep Learning for Free Energy Profiling.

Hung N DoJinan WangApurba BhattaraiYinglong Miao
Published in: Journal of chemical theory and computation (2022)
We introduce a Gaussian-accelerated molecular dynamics (GaMD), deep learning (DL), and free energy profiling workflow (GLOW) to predict molecular determinants and map free energy landscapes of biomolecules. All-atom GaMD-enhanced sampling simulations are first performed on biomolecules of interest. Structural contact maps are then calculated from GaMD simulation frames and transformed into images for building DL models using a convolutional neural network. Important structural contacts are further determined from DL models of attention maps of the structural contact gradients, which allow us to identify the system reaction coordinates. Finally, free energy profiles are calculated for the selected reaction coordinates through energetic reweighting of the GaMD simulations. We have also successfully demonstrated GLOW for the characterization of activation and allosteric modulation of a G protein-coupled receptor, using the adenosine A 1 receptor (A 1 AR) as a model system. GLOW findings are highly consistent with previous experimental and computational studies of the A 1 AR, while also providing further mechanistic insights into the receptor function. In summary, GLOW provides a systematic approach to mapping free energy landscapes of biomolecules. The GLOW workflow and its user manual can be downloaded at http://miaolab.org/GLOW.
Keyphrases
  • molecular dynamics
  • deep learning
  • convolutional neural network
  • density functional theory
  • artificial intelligence
  • electronic health record
  • machine learning
  • single cell
  • small molecule
  • high density
  • case control