WikiSysop: Created page with "== Citation == Barchet, Charles / Fréchin, Léo / Holvec, Samuel / Hazemann, Isabelle / von Loeffelholz, Ottilie / Klaholz, Bruno P. Focused classifications and refinements..."

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Created page with "== Citation == Barchet, Charles / Fréchin, Léo / Holvec, Samuel / Hazemann, Isabelle / von Loeffelholz, Ottilie / Klaholz, Bruno P. Focused classifications and refinements..."

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== Citation ==

Barchet, Charles / Fréchin, Léo / Holvec, Samuel / Hazemann, Isabelle / von Loeffelholz, Ottilie / Klaholz, Bruno P. Focused classifications and refinements in high-resolution single particle cryo-EM analysis. 2023. Journal of Structural Biology, Vol. 215, No. 4, p. 108015

== Abstract ==

Recent advances in cryo electron microscopy (cryo-EM) and image processing provide new opportunities to
analyse drug targets at high resolution. However, structural heterogeneity limits resolution in many practical
cases, hence restricting the level at which structural details can be analysed and drug design be performed. As
structural disorder is not spread throughout the entire structure of a given macromolecular complex but instead
is found in certain regions that move with respect to others and covering molecular scales from domain
conformational changes up to the level of side chain conformations in ligand binding pockets, it is possible to
focus the attention on those regions and the associated relative movements. Here we show how the usage of
focused classifications and refinements provide insights into global conformational arrangements, exemplified on
the human ribosome and on the cannabinoid G protein coupled receptor (GPCR), and how they can improve the
local map resolution from an essentially disordered region to the 3–4 Å and finally to the 2 Å resolution range. A
systematic analysis with variable spherical masks during focused refinement is presented showing that the choice
of an optimal mask size helps refining to high resolution. This study covers several practical approaches on 4
examples illustrating how important mask size & shape and including neighbouring structural elements are for a
focused analysis of a macromolecular complex. Such methods will be crucial for cryo-EM structure-based drug
design of various medical targets and are applicable to single particle cryo-EM and electron tomography data.

== Keywords ==

== Links ==

https://www.sciencedirect.com/science/article/pii/S1047847723000783

== Related software ==

== Related methods ==

== Comments ==

2023Barchet Focused - Revision history

WikiSysop: Created page with "== Citation == Barchet, Charles / Fréchin, Léo / Holvec, Samuel / Hazemann, Isabelle / von Loeffelholz, Ottilie / Klaholz, Bruno P. Focused classifications and refinements..."