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PreprintCC BYChemRxiv

Achieving Sustained Conformational Exploration with Continually Adaptive Local Memory Sampling

  • Steven L. Austin1,2
  • H. Lee Woodcock3,4
4 affiliations
  1. 1Division of Natural Sciences
  2. 2New College of Florida
  3. 3Department of Chemistry
  4. 4University of South Florida
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Abstract

Enhanced sampling techniques aim to expedite the exploration of molecular conformations and their associated transitions. The extended adaptive biasing force method (eABF) is an enhanced sampling technique that applies a biasing force to targeted collective variables (CV), which serves to overcome energy barriers that would normally delay conformational transitions. With eABF, the biasing force is adaptively constructed to nullify the average force acting along the CV, effectively removing barriers to promote accelerated transitions. However, the eABF biasing force can become unresponsive to CV-coupled environmental dynamics, leading to hindered CV sampling. Therefore, in order to promote persistent CV transitions, we developed the continually adaptive local memory (CALM) sampling method, designed to sustain adaptation of the eABF biasing force. This is achieved by maintaining a limited sampling memory, which allows for CV moves to continually synchronize with coupled environmental dynamics. Herein, we show CALM effectively accelerates conformational sampling of alanine dipeptide and deca-alanine in vacuum and also deca-alanine and the mini-protein chignolin in explicit water. As a result of maintaining biasing force adaptability, we illustrate how CALM promotes sustained CV transitions via access to hidden conformational pathways that are not accessible via eABF.

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Cite

BibTeXRIS
BibTeX
@misc{austin2026achieving,
  title = {{Achieving Sustained Conformational Exploration with Continually Adaptive Local Memory Sampling}},
  author = {Steven L. Austin and H. Lee Woodcock},
  howpublished = {ChemRxiv},
  year = {2026},
  month = sep,
  doi = {10.26434/chemrxiv.15008813/v1},
  url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008813/v1},
  note = {CC BY},
}
RIS
TY  - UNPB
TI  - Achieving Sustained Conformational Exploration with Continually Adaptive Local Memory Sampling
AU  - Steven L. Austin
AU  - H. Lee Woodcock
PY  - 2026
DA  - 2026/09/14
PB  - ChemRxiv
DO  - 10.26434/chemrxiv.15008813/v1
UR  - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008813/v1
AB  - Enhanced sampling techniques aim to expedite the exploration of molecular conformations and their associated transitions. The extended adaptive biasing force method (eABF) is an enhanced sampling technique that applies a biasing force to targeted collective variables (CV), which serves to overcome energy barriers that would normally delay conformational transitions. With eABF, the biasing force is adaptively constructed to nullify the average force acting along the CV, effectively removing barriers to promote accelerated transitions. However, the eABF biasing force can become unresponsive to CV-coupled environmental dynamics, leading to hindered CV sampling. Therefore, in order to promote persistent CV transitions, we developed the continually adaptive local memory (CALM) sampling method, designed to sustain adaptation of the eABF biasing force. This is achieved by maintaining a limited sampling memory, which allows for CV moves to continually synchronize with coupled environmental dynamics. Herein, we show CALM effectively accelerates conformational sampling of alanine dipeptide and deca-alanine in vacuum and also deca-alanine and the mini-protein chignolin in explicit water. As a result of maintaining biasing force adaptability, we illustrate how CALM promotes sustained CV transitions via access to hidden conformational pathways that are not accessible via eABF.
ER  -