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1. IgStrand: A universal residue numbering scheme for the immunoglobulin-fold (Ig-fold) to study Ig-proteomes and Ig-interactomes

   https://doi.org/10.1371/journal.pcbi.1012813  

   Tawfeeq, Caesar; Wang, Jiyao; Khaniya, Umesh; Madej, Thomas; Song, James; Abrol, Ravinder; Youkharibache, Philippe (April 2025, PLOS Computational Biology)

   Friedberg, Iddo (Ed.)

   The Immunoglobulin fold (Ig-fold) is found in proteins from all domains of life and represents the most populous fold in the human genome, with current estimates ranging from 2 to 3% of protein coding regions. That proportion is much higher in the surfaceome where Ig and Ig-like domains orchestrate cell-cell recognition, adhesion and signaling. The ability of Ig-domains to reliably fold and self-assemble through highly specific interfaces represents a remarkable property of these domains, making them key elements of molecular interaction systems: the immune system, the nervous system, the vascular system and the muscular system. We define a universal residue numbering scheme, common to all domains sharing the Ig-fold in order to study the wide spectrum of Ig-domain variants constituting the Ig-proteome and Ig-Ig interactomes at the heart of thesesystems. The “IgStrand numbering scheme” enables the identification of Ig structural proteomes and interactomes in and between any species, and comparative structural, functional, and evolutionary analyses. We review how Ig-domains are classified today as topological and structural variants and highlight the“Ig-fold irreducible structural signature”shared by all of them. The IgStrand numbering scheme lays the foundation for the systematic annotation of structural proteomes by detecting and accurately labeling Ig-, Ig-like and Ig-extended domains in proteins, which are poorly annotated in current databases and opens the door to accurate machine learning. Importantly, it sheds light on the robustIg protein folding algorithmused by nature to form beta sandwich supersecondary structures. The numbering scheme powers an algorithm implemented in the interactive structural analysis software iCn3D to systematically recognize Ig-domains, annotate them and perform detailed analyses comparing any domain sharing the Ig-fold in sequence, topology and structure, regardless of their diverse topologies or origin. The scheme provides a robust fold detection and labeling mechanism that reveals unsuspected structural homologies among protein structures beyond currently identified Ig- and Ig-like domain variants. Indeed, multiple folds classified independently contain a common structural signature, in particular jelly-rolls. Examples of folds that harbor an “Ig-extended” architecture are given. Applications in protein engineering around the Ig-architecture are straightforward based on the universal numbering. 

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2. The Institutional Grammar: A Method for Coding Institutions and its Potential for Advancing Third Sector Research

   https://doi.org/10.1007/s11266-021-00423-w  

   Bushouse, B; Schweik, C.; Siddiki, S.; Rice, D.; Wolfson, I. (October 2021, Voluntas)

   Institutions—defined as strategies, norms and rules (Ostrom Understanding institutional diversity, Princeton University Press, Princeton, 2005)—are omnipresent in third sector contexts. In this paper, we present the Institutional Grammar (IG) as a theoretically informed approach to support institutional analysis in third sector research. More specifically, the IG coding syntax allows the researcher to systematically wade through rich text and (transcribed) spoken language to identify and dissect institutional statements into finer syntactical segments of interest to the researcher. It is a versatile method that can generate data for small- or large-N research projects and can be integrated with mixed-method research designs. After first introducing and describing the IG, we present a case study to illustrate how a IG-based syntactic analysis can be leveraged to inform third sector research. In the case, we ask: Do the rules embedded in regulatory text addressing the involuntary dissolution of charity organizations differ between bifurcated and unitary jurisdictions in the United States? Using IG’s ABDICO 2.0 syntax, we identify eleven “Activation Condition” (AC) categories that trigger action and assess variation among the 46 jurisdictions. We ultimately conclude that the rules do not differ between bifurcated and unitary jurisdictions, but that finding is not the primary concern. The case demonstrates IG as an important methodological advance that yields granular, structured analyses of rules, norms and strategies in third sector settings that may be difficult to identify with other methods. We then emphasize four areas of third sector research that could benefit from the addition of IG-based methods: analysis of (1) rule compliance, (2) inter-organizational collaboration, (3) comparative study of institutional design, and (4) the study of institutional change. We close the paper with some reflections on where IG-based analysis is headed. 

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3. The Use of the Institutional Grammar 1.0 for Institutional Analysis: A Literature Review

   https://doi.org/10.5334/ijc.1214  

   Pieper, Leah; Virgüez, Santiago; Schlager, Edella; Schweik, Charlie (February 2023, International Journal of the Commons)

   Since Crawford and Ostrom proposed the Institutional Grammar (IG), a conceptual tool for breaking down and organizing institutional statements, a burgeoning literature has used it to study institutions contained in single documents and to conduct comparative institutional analysis across multiple countries and time periods. Moreover, rapid advances in text analysis and computational methods are creating new analytic opportunities to study rules, norms and strategies by leveraging the IG syntax. At this stage, it is important to assess the existing literature to understand how the IG has supported institutional analysis across a variety of contexts, including commons governance. Based on a corpus of 48 empirical articles published between 2010 and 2021, we explore how analysts have operationalized institutional statements using the IG. We also synthesize the IG-based metrics and theoretical concepts developed in these articles to illustrate the contributions of IG for measurement of challenging concepts such as polycentricity, discretion, and compliance, among others. Our findings indicate that the IG is a flexible and adaptable tool for institutional analysis, especially for making empirical contributions from text-based data, and it holds promise toward building a potentially new emerging subfield we call Computational Institutional Analysis. 

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4. Validated determination of NRG1 Ig-like domain structure by mass spectrometry coupled with computational modeling

   https://doi.org/10.1038/s42003-022-03411-y  

   Khaje, Niloofar Abolhasani; Eletsky, Alexander; Biehn, Sarah E.; Mobley, Charles K.; Rogals, Monique J.; Kim, Yoonkyoo; Mishra, Sushil K.; Doerksen, Robert J.; Lindert, Steffen; Prestegard, James H.; et al (May 2022, Communications Biology)

   Abstract High resolution hydroxyl radical protein footprinting (HR-HRPF) is a mass spectrometry-based method that measures the solvent exposure of multiple amino acids in a single experiment, offering constraints for experimentally informed computational modeling. HR-HRPF-based modeling has previously been used to accurately model the structure of proteins of known structure, but the technique has never been used to determine the structure of a protein of unknown structure. Here, we present the use of HR-HRPF-based modeling to determine the structure of the Ig-like domain of NRG1, a protein with no close homolog of known structure. Independent determination of the protein structure by both HR-HRPF-based modeling and heteronuclear NMR was carried out, with results compared only after both processes were complete. The HR-HRPF-based model was highly similar to the lowest energy NMR model, with a backbone RMSD of 1.6 Å. To our knowledge, this is the first use of HR-HRPF-based modeling to determine a previously uncharacterized protein structure. 

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5. Machine Coding with the Institutional Grammar

   Kwon, Hyoung-Keun; Sawyer, Adam; Frey, Seth; Siddiki, Saba; Rice, Douglas (June 2020, The Institutional Grammar Workshop)

   The Institutional Grammar (IG) is used to analyze the syntactic structure of statements constituting institutions (e.g., public policy and social norms) that indicate behavioral constraints. Significant progress has been made in methodologically developing the IG in recent years. Scholars have offered increasingly clear guidelines for IG-based coding, identified unique considerations for applying the IG to different types of institutions, and even expanded its syntactic scope. However, while validated as a robust institutional analysis approach, the resource and time commitment associated with its application has precipitated concerns over whether the IG might ever enjoy widespread use. Needed now in the methodological development of the IG are reliable and accessible (i.e., open source) approaches that reduce the costs associated with its application. We propose an automated approach leveraging computational text analysis and natural language processing. We then present results from an evaluation in the context of food system regulations. 

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