ArticleJournal of chemical information and modeling2025
A Self-Consistent Approach to Rotamer and Protonation State Assignments (RAPA): Moving Beyond Single Protein Configurations.
Article in Journal of chemical information and modeling, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
Abstract
There are currently over 160,000 protein crystal structures obtained by X-ray diffraction with resolutions of 1.5 Å or greater in the Protein Data Bank. At these resolutions hydrogen atoms do not resolve and heavy atoms such as oxygen, carbon, and nitrogen are indistinguishable. This leads to ambiguity in the rotamer and protonation states of multiple amino acids, notably asparagine, glutamine, histidine, serine, tyrosine, and threonine. When the rotamer and protonation states of these residues change, so too does the electrochemical surface of a binding site. A variety of computational approaches have been developed to assign states for these residues by investigating all possibilities and typically deciding on a single rotamer or protonation state for each residue that is consistent with the crystal structure. Here, we posit that there are multiple rotamer and protonation states that are consistent with the resolved structure of the proteins and introduce a Rotamer and Protonation Assignment (RAPA) protocol which analyzes local hydrogen-bonding environments in the resolved structures of proteins and identifies a set of unique rotamer and protonation states that are energetically consistent with the experimentally reported crystal structure. We evaluate the RAPA-predicted configurations in molecular dynamics simulations and find that there are multiple configurations for each protein that maintain structures consistent with the X-ray results. In our initial evaluations of the RAPA protocol, we find that for most proteins (69/77) there are multiple energetically accessible rotamer and protonation state configurations however the total number is limited to 8 or fewer for most of the proteins (62 of 77). This suggests that there is no combinatorial explosion in the number of energetically accessible rotamer and protonation states for most proteins and investigating all such states is computationally feasible.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.