WikiSysop: Created page with "== Citation == Matsuoka, D., Sugita, Y. and Mori, T. 2025. An Empirical Biasing Force Constant to Minimize Overfitting in Cryo-EM Flexible Fitting Refinement. J. Chemical Information and Modelling. (2025). == Abstract == Reliable modeling of protein structures from a cryo- EM density map is one of the central issues in structural biology. Typically, the constructed model is refined using a flexible fitting method combined with molecular dynamics, where a biasing poten..."

2025-09-22T16:23:26Z

Created page with "== Citation == Matsuoka, D., Sugita, Y. and Mori, T. 2025. An Empirical Biasing Force Constant to Minimize Overfitting in Cryo-EM Flexible Fitting Refinement. J. Chemical Information and Modelling. (2025). == Abstract == Reliable modeling of protein structures from a cryo- EM density map is one of the central issues in structural biology. Typically, the constructed model is refined using a flexible fitting method combined with molecular dynamics, where a biasing poten..."

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== Citation ==

Matsuoka, D., Sugita, Y. and Mori, T. 2025. An Empirical Biasing Force Constant to Minimize Overfitting in Cryo-EM Flexible Fitting Refinement. J. Chemical Information and Modelling. (2025).

== Abstract ==

Reliable modeling of protein structures from a cryo-
EM density map is one of the central issues in structural biology.
Typically, the constructed model is refined using a flexible fitting
method combined with molecular dynamics, where a biasing
potential is introduced to guide the protein structure toward the
density map. However, the appropriate force constant for the
biasing potential is generally unknown a priori. Here, we propose
an empirical force constant that enables flexible fitting refinement
with minimal overfitting. The rule is derived from systematic
flexible fitting calculations performed on 29 selected systems (map
resolution = 3.0−6.8 Å) using a range of force constants from weak
to strong values. The refined structures are evaluated based on the
MolProbity score and secondary-structure-forming tendencies. Our
analysis shows that in most systems, the MolProbity score increases monotonically as the force constant increases. In addition, α-
helix and β-strand tend to collapse beyond a certain force constant depending on the system size or number of fitting atoms (Natom).
Based on these findings, we propose that a suitable choice for the biasing force constant in the cross-correlation coefficient-based
flexible fitting refinement is 3Natom kcal/mol. This provides a practical guideline for an initial selection of the force constant, aiding in
the search for a more suitable value and serving as a useful default parameter in flexible fitting protocols to achieve reliable models
with minimal overfitting.

== Keywords ==

== Links ==

https://pubs.acs.org/doi/full/10.1021/acs.jcim.5c01424

== Related software ==

== Related methods ==

== Comments ==

2025Matsuoka ForceConstant - Revision history