Instruct: Identify the main category of Biorxiv papers based on the titles and abstracts
Query: Structural and temporal basis for agonism in the α4β2 nicotinic acetylcholine receptor Despite decades of study, the structural mechanisms underpinning agonist efficacy in pentameric ligand-gated ion channels remain poorly understood. Here, a combination of extensive equilibrium and dynamical-nonequilibrium molecular dynamics simulations was used to obtain a detailed description of the structural and dynamic changes induced within the human 4{beta}2 nicotinic acetylcholine receptor by a full and a partial agonist, namely acetylcholine and nicotine, and map how these rearrangements propagate within this receptor. These simulations reveal how the agonists modulate the patterns associated with intra and inter-domain communication and the evolution of the agonist-specific structural rearrangements. For the first time, we show that full and partial agonists, although generally using similar routes for through-receptor signal transmission, induce different amplitudes of conformational rearrangements in key functional motifs, thus impacting the rates of signal propagation within the protein. The largest agonist-induced conformational differences are located in the Cys loop, loops C and 1-{beta}1 in the 4 subunit, loops F and {beta}1-{beta}2 in the {beta}2 subunit and in the extracellular selectivity filter.
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The categories of this paper are: microbiology
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The categories of this paper are: immunology
29
The categories of this paper are: education
14
The categories of this paper are: biophysics
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The categories of this paper are: behavior
32
The categories of this paper are: zoology
9
The categories of this paper are: synthetic
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The categories of this paper are: pharmacology
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The categories of this paper are: and
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The categories of this paper are: ecology
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The categories of this paper are: bioengineering
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The categories of this paper are: cell
31
The categories of this paper are: paleontology
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The categories of this paper are: molecular
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The categories of this paper are: pathology
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The categories of this paper are: developmental