Post-translational Modification Sites Research Articles

Immunological lectins in shrimp Penaeus vannamei challenged with infectious myonecrosis virus (IMNV) under low-salinity conditions

Lectins are proteins capable of recognizing and binding to glycan in a specific way. In invertebrates, lectins are a crucial group of Pattern Recognition Proteins (PRRs), activating cellular and humoral responses in the innate immune system. The shrimp Penaeus vannamei is the main crustacean cultivated worldwide, however, the productivity of cultures is strongly affected by diseases, mainly viral ones, such as Infectious Myonecrosis (IMN). Thus, we investigated the participation of five lectins (LvAV, LvCTL4, LvCTL5, LvCTLU, and LvLdlrCTL) in IMNV-challenged shrimp. We verified upregulation gene profiles of lectins after IMNV-challenge, especially in hepatopancreas and gills, in addition to an increase in total hemocytes count (THC) after to 12 h post-infection (hpi). The bioinformatics characterization also revealed several sites of post-translational modification (PTM), such as phosphorylation and glycosylation, which possibly influence the action and stabilization of these lectins. We conclude that LvLdlrCTL and LvCTL5 are the lectins with greater participation in the activation of the immune system against IMNV, showing the greatest potential for PTM, higher upregulation levels, and overlapping with the THC and IMNV viral load.

Post-translational modifications of proteins in cardiovascular diseases examined by proteomic approaches.

Over 400 different types of post-translational modifications (PTMs) have been reported and over 200 various types of PTMs have been discovered using mass spectrometry (MS)-based proteomics. MS-based proteomics has proven to be a powerful method capable of global PTM mapping with the identification of modified proteins/peptides, the localization of PTM sites and PTM quantitation. PTMs play regulatory roles in protein functions, activities and interactions in various heart related diseases, such as ischemia/reperfusion injury, cardiomyopathy and heart failure. The recognition of PTMs that are specific to cardiovascular pathology and the clarification of the mechanisms underlying these PTMs at molecular levels are crucial for discovery of novel biomarkers and application in a clinical setting. With sensitive MS instrumentation and novel biostatistical methods for precise processing of the data, low-abundance PTMs can be successfully detected and the beneficial or unfavorable effects of specific PTMs on cardiac function can be determined. Moreover, computational proteomic strategies that can predict PTM sites based on MS data have gained an increasing interest and can contribute to characterization of PTM profiles in cardiovascular disorders. More recently, machine learning- and deep learning-based methods have been employed to predict the locations of PTMs and explore PTM crosstalk. In this review article, the types of PTMs are briefly overviewed, approaches for PTM identification/quantitation in MS-based proteomics are discussed and recently published proteomic studies on PTMs associated with cardiovascular diseases are included.

IsoForma: An R Package for Quantifying and Visualizing Positional Isomers in Top-Down LC-MS/MS Data.

Proteoforms, the different forms of a protein with sequence variations including post-translational modifications (PTMs), execute vital functions in biological systems, such as cell signaling and epigenetic regulation. Advances in top-down mass spectrometry (MS) technology have permitted the direct characterization of intact proteoforms and their exact number of modification sites, allowing for the relative quantification of positional isomers (PI). Protein positional isomers refer to a set of proteoforms with identical total mass and set of modifications, but varying PTM site combinations. The relative abundance of PI can be estimated by matching proteoform-specific fragment ions to top-down tandem MS (MS2) data to localize and quantify modifications. However, the current approaches heavily rely on manual annotation. Here, we present IsoForma, an open-source R package for the relative quantification of PI within a single tool. Benchmarking IsoForma's performance against two existing workflows produced comparable results and improvements in speed. Overall, IsoForma provides a streamlined process for quantifying PI, reduces the analysis time, and offers an essential framework for developing customized proteoform analysis workflows. The software is open source and available at https://github.com/EMSL-Computing/isoforma-lib.

Full-length single-molecule protein fingerprinting.

Proteins are the primary functional actors of the cell. While proteoform diversity is known to be highly biologically relevant, current protein analysis methods are of limited use for distinguishing proteoforms. Mass spectrometric methods, in particular, often provide only ambiguous information on post-translational modification sites, and sequences of co-existing modifications may not be resolved. Here we demonstrate fluorescence resonance energy transfer (FRET)-based single-molecule protein fingerprinting to map the location of individual amino acids and post-translational modifications within single full-length protein molecules. Our data show that both intrinsically disordered proteins and folded globular proteins can be fingerprinted with a subnanometer resolution, achieved by probing the amino acids one by one using single-molecule FRET via DNA exchange. This capability was demonstrated through the analysis of alpha-synuclein, an intrinsically disordered protein, by accurately quantifying isoforms in mixtures using a machine learning classifier, and by determining the locations of two O-GlcNAc moieties. Furthermore, we demonstrate fingerprinting of the globular proteins Bcl-2-like protein 1, procalcitonin and S100A9. We anticipate that our ability to perform proteoform identification with the ultimate sensitivity may unlock exciting new venues in proteomics research and biomarker-based diagnosis.

Post-translational modification sites are present in hydrophilic cavities of alpha-synuclein, tau, FUS, and TDP-43 fibrils: A molecular dynamics study

Post-translational modification sites are present in hydrophilic cavities of alpha-synuclein, tau, FUS, and TDP-43 fibrils: A molecular dynamics study

DeepPTM: Protein Post-translational Modification Prediction from Protein Sequences by Combining Deep Protein Language Model with Vision Transformers

Introduction:: More recent self-supervised deep language models, such as Bidirectional Encoder Representations from Transformers (BERT), have performed the best on some language tasks by contextualizing word embeddings for a better dynamic representation. Their proteinspecific versions, such as ProtBERT, generated dynamic protein sequence embeddings, which resulted in better performance for several bioinformatics tasks. Besides, a number of different protein post-translational modifications are prominent in cellular tasks such as development and differentiation. The current biological experiments can detect these modifications, but within a longer duration and with a significant cost. Methods:: In this paper, to comprehend the accompanying biological processes concisely and more rapidly, we propose DEEPPTM to predict protein post-translational modification (PTM) sites from protein sequences more efficiently. Different than the current methods, DEEPPTM enhances the modification prediction performance by integrating specialized ProtBERT-based protein embeddings with attention-based vision transformers (ViT), and reveals the associations between different modification types and protein sequence content. Additionally, it can infer several different modifications over different species. Results:: Human and mouse ROC AUCs for predicting Succinylation modifications were 0.988 and 0.965 respectively, once 10-fold cross-validation is applied. Similarly, we have obtained 0.982, 0.955, and 0.953 ROC AUC scores on inferring ubiquitination, crotonylation, and glycation sites, respectively. According to detailed computational experiments, DEEPPTM lessens the time spent in laboratory experiments while outperforming the competing methods as well as baselines on inferring all 4 modification sites. In our case, attention-based deep learning methods such as vision transformers look more favorable to learning from ProtBERT features than more traditional deep learning and machine learning techniques. Conclusion:: Additionally, the protein-specific ProtBERT model is more effective than the original BERT embeddings for PTM prediction tasks. Our code and datasets can be found at https://github.com/seferlab/deepptm.

Acetylated tau exacerbates apoptosis by disturbing mitochondrial dynamics in HEK293 cells.

An increase in tau acetylation at K274 and K281 and abnormal mitochondrial dynamics have been observed in the brains of Alzheimer's disease (AD) patients. Here, we constructed three types of tau plasmids, TauKQ (acetylated tau mutant, by mutating its K274/K281 into glutamine to mimic disease-associated lysine acetylation), TauKR (non-acetylated tau mutant, by mutating its K274/K281 into arginine), and TauWT (wild-type human full-length tau). By transfecting these tau plasmids in HEK293 cells, we found that TauWT and TauKR induced mitochondrial fusion by increasing the level of mitochondrial fusion proteins. Conversely, TauKQ induced mitochondrial fission by reducing mitochondrial fusion proteins, exacerbating mitochondrial dysfunction and apoptosis. BGP-15 ameliorated TauKQ-induced mitochondrial dysfunction and apoptosis by improving mitochondrial dynamics. Our findings suggest that acetylation of K274/281 represents an important post-translational modification site regulating mitochondrial dynamics, and that BGP-15 holds potential as a therapeutic agent for mitochondria-associated diseases such as AD.

MERITS: a web-based integrated Mycobacterial PE/PPE protein database.

PE/PPE proteins, highly abundant in the Mycobacterium genome, play a vital role in virulence and immune modulation. Understanding their functions is key to comprehending the internal mechanisms of Mycobacterium. However, a lack of dedicated resources has limited research into PE/PPE proteins. Addressing this gap, we introduce MycobactERIal PE/PPE proTeinS (MERITS), a comprehensive 3D structure database specifically designed for PE/PPE proteins. MERITS hosts 22 353 non-redundant PE/PPE proteins, encompassing details like physicochemical properties, subcellular localization, post-translational modification sites, protein functions, and measures of antigenicity, toxicity, and allergenicity. MERITS also includes data on their secondary and tertiary structure, along with other relevant biological information. MERITS is designed to be user-friendly, offering interactive search and data browsing features to aid researchers in exploring the potential functions of PE/PPE proteins. MERITS is expected to become a crucial resource in the field, aiding in developing new diagnostics and vaccines by elucidating the sequence-structure-functional relationships of PE/PPE proteins. MERITS is freely accessible at http://merits.unimelb-biotools.cloud.edu.au/.

FLAMS: Find Lysine Acylations and other Modification Sites.

Today, hundreds of post-translational modification (PTM) sites are routinely identified at once, but the comparison of new experimental datasets to already existing ones is hampered by the current inability to search most PTM databases at the protein residue level. We present FLAMS (Find Lysine Acylations and other Modification Sites), a Python3-based command line and web-tool that enables researchers to compare their PTM sites to the contents of the CPLM, the largest dedicated protein lysine modification database, and dbPTM, the most comprehensive general PTM database, at the residue level. FLAMS can be integrated into PTM analysis pipelines, allowing researchers to quickly assess the novelty and conservation of PTM sites across species in newly generated datasets, aiding in the functional assessment of sites and the prioritization of sites for further experimental characterization. FLAMS is implemented in Python3, and freely available under an MIT license. It can be found as a command line tool at https://github.com/hannelorelongin/FLAMS, pip and conda; and as a web service at https://www.biw.kuleuven.be/m2s/cmpg/research/CSB/tools/flams/.

In Silico Analysis of the ROP29 Protein as a Vaccine Candidate Against Toxoplasma gondii.

The progression of Toxoplasma gondii (T. gondii) invasion is aided by rhoptry proteins (ROPs), which are also crucial for the parasite's survival in host cells. In this study, in silico analysis was performed to examine the various aspects of the ROP29 protein, such as physicochemical properties, potential T- and B-cell epitopes, and other significant features. The research revealed that there were 55 possible sites for posttranslational modification in the ROP29 protein. The secondary structure of the ROP29 protein consists of a random coil, an alpha-helix, and an extended strand, which account for 49.69%, 36.81%, and 13.50%, respectively. Moreover, a number of putative T- and B-cell epitopes for ROP29 were found. The Ramachandran plot showed that 88.91% (crude model) and 97.54% (refine model) of the amino acid residues were located in the favored regions. Also, the testing of this protein's antigenicity and allergenicity showed that it was nonallergenic and immunogenic. Our results suggested that employing in silico tools to apply structural and functional predictions to the ROP29 protein can lower the likelihood that laboratory investigations will fail. This research served as a crucial foundation for further research. More research is required in the future in suitable animal model employing ROP29 alone or in combination with other antigens.

Stress and the domestic cat: have humans accidentally created an animal mimic of neurodegeneration?

Many neurodegenerative diseases (NDD) appear to share commonality of origin, chronic ER stress. The endoplasmic reticulum (ER) is a dynamic organelle, functioning as a major site of protein synthesis and protein posttranslational modifications, required for proper folding. ER stress can occur because of external stimuli, such as oxidative stress or neuroinflammatory cytokines, creating the ER luminal environment permissive for the accumulation of aggregated and misfolded proteins. Unresolvable ER stress upregulates a highly conserved pathway, the unfolded protein response (UPR). Maladaptive chronic activation of UPR components leads to apoptotic neuronal death. In addition to other factors, physiological responses to stressors are emerging as a significant risk factor in the etiology and pathogenesis of NDD. Owned cats share a common environment with people, being exposed to many of the same stressors as people and additional pressures due to their "quasi" domesticated status. Feline Cognitive Dysfunction Syndrome (fCDS) presents many of the same disease hallmarks as human NDD. The prevalence of fCDS is rapidly increasing as more people welcome cats as companions. Barely recognized 20 years ago, veterinarians and scientists are in infancy stages in understanding what is a very complex disease. This review will describe how cats may represent an unexplored animal mimetic phenotype for human NDD with stressors as potential triggering mechanisms. We will consider how multiple variations of stressful events over the short-life span of a cat could affect neuronal loss or glial dysfunction and ultimately tip the balance towards dementia.

Semi-ssPTM: A Web Server for Species-Specific Lysine Post-Translational Modification Site Prediction by Semi-Supervised Domain Adaptation

Semi-ssPTM: A Web Server for Species-Specific Lysine Post-Translational Modification Site Prediction by Semi-Supervised Domain Adaptation

Comprehensive bioinformatics-based annotation and functional characterization of bovine chymosin protein revealed novel biological insights

Chymosin, an aspartic protease present in the stomachs of young ruminants like cows (bovine), causes milk coagulation and cheese production through the breakdown of κ-casein peptide bonds at the Met105-Phe106 site. Bovine chymosin is first synthesized as a pre-prochymosin that is cleaved to produce the mature chymosin protein. Despite significant strides in research, our understanding of this crucial enzyme remains incomplete. The purpose of this work was to perform in silico evolutionary and functional analysis and to gain unique insights into the structure of this protein. For this, the sequence of Bos taurus chymosin from UniProt database was subjected to various bioinformatics analyses. We found that bovine chymosin is a low molecular weight and hydrophilic protein that has homologs in other Bovidae species. Two active sites of aspartic peptidases, along with a functional domain, were identified. Gene Ontology analysis further confirmed chymosin's involvement in proteolysis and aspartic endopeptidase activity. Potential disordered residues and post-translational modification sites were also uncovered. It was revealed that the secondary structure of bovine chymosin is comprised of beta strands (44.27%), coils (43.65%), and alpha helices (12.07%). A highly optimized 3D structure was also obtained. Moreover, crucial protein–protein interactions were unveiled. Altogether, these findings provide valuable insights that could guide future research on bovine chymosin and its biological roles.

Molecular cloning, expression and Insilco analysis of drought stress inducible MYB transcription factor encoding gene from C4 plant Eleusine coracana

Drought is one of the key abiotic stresses that critically influences the crops by restraining their growth and yield potential. Being sessile, plant tackle the detrimental effects of drought stress by modulating the cellular state by changing the gene expression. The transcriptional syndicate essentially drives such alteration of gene expression. Transcription factors (TF) are the key regulatory protein that controls the expression of their target gene by binding to the cis-regulatory elements present in the promoter region. Myb-TF, ubiquitously present in all eukaryotes belong to one of the largest TF family, and play a wide array of biological functions in plants, including anthocyanin biosynthesis, vasculature system, cell signalling, seed maturation and abiotc stress responses. The present performed isolation and molecular cloning of full length Myb TF from Eleusine corocana. The isolated full-length coding sequence has 1053 bp and 350 aa was submitted to NCBI (Accession number MT312253). The transcript level of EcMYB increases under different abiotic stress treatments including dehydration, salinity, and high-temperature stress. The promoter region of EcMyb1 was found to be enriched in stress-responsive cis-regulatory elements such as DRE, HSE, ABRE etc. In phylogenetic analysis, EcMyb1 appeared to have high homology with its monocot orthologs particularly Sateria italica, Hordeum vulgare, Saccharum barberi and Oryza sativa. The three-dimension protein structure was generated based on homology modeling and structural aspects were discussed. Further, Insilco analysis was conducted to explore the physiological properties, subcellular localization, potential posttranslational modification sites (phosphorylation and glycosylation sites), and molecular and biological function of the full-length protein. Overall, the expression profiling and Insilco analysis of EcMyb1 strongly indicated its potential role in abiotic stress response in Eleusine corocana.

The tubulin database: Linking mutations, modifications, ligands and local interactions.

Microtubules are polymeric filaments, constructed of α-β tubulin heterodimers that underlie critical subcellular structures in eukaryotic organisms. Four homologous proteins (γ-, δ-, ε- and ζ-tubulin) additionally contribute to specialized microtubule functions. Although there is an immense volume of publicly available data pertaining to tubulins, it is difficult to assimilate all potentially relevant information across diverse organisms, isotypes, and categories of data. We previously assembled an extensive web-based catalogue of published missense mutations to tubulins with >1,500 entries that each document a specific substitution to a discrete tubulin, the species where the mutation was described and the associated phenotype with hyperlinks to the amino acid sequence and citation(s) for research. This report describes a significant update and expansion of our online resource (TubulinDB.bio.uci.edu) to nearly 18,000 entries. It now encompasses a cross-referenced catalog of post-translational modifications (PTMs) to tubulin drawn from public datasets, primary literature, and predictive algorithms. In addition, tubulin protein structures were used to define local interactions with bound ligands (GTP, GDP and diverse microtubule-targeting agents) and amino acids at the intradimer interface, within the microtubule lattice and with associated proteins. To effectively cross-reference these datasets, we established a universal tubulin numbering system to map entries into a common framework that accommodates specific insertions and deletions to tubulins. Indexing and cross-referencing permitted us to discern previously unappreciated patterns. We describe previously unlinked observations of loss of PTM sites in the context of cancer cells and tubulinopathies. Similarly, we expanded the set of clinical substitutions that may compromise MAP or microtubule-motor interactions by collecting tubulin missense mutations that alter amino acids at the interface with dynein and doublecortin. By expanding the database as a curated resource, we hope to relate model organism data to clinical findings of pathogenic tubulin variants. Ultimately, we aim to aid researchers in hypothesis generation and design of studies to dissect tubulin function.

Bioinformatic analysis of THAP9 transposase homolog: conserved regions, novel motifs

THAP9 is a transposable element-derived gene that encodes the THAP9 protein, which is homologous to the Drosophila P-element transposase (DmTNP) and can cut and paste DNA. However, the exact functional role of THAP9 is unknown. Here, we perform structure prediction, evolutionary analysis and extensive in silico characterization of THAP9, including predicting domains and putative post-translational modification sites. Comparison of the AlphaFold-predicted structure of THAP9 with the DmTNP CryoEM structure, provided insights about the C2CH motif and other DNA binding residues, RNase H-like catalytic domain and insertion domain of the THAP9 protein. We also predicted previously unreported mammalian-specific post-translational modification sites that may play a role in the subcellular localization of THAP9. Furthermore, we observed that there are distinct organism class-specific conservation patterns of key functional residues in certain THAP9 domains.

In Silico Evaluation of Coding and Non-Coding nsSNPs in the Thrombopoietin Receptor (MPL) Proto-Oncogene: Assessing Their Influence on Protein Stability, Structure, and Function.

The thrombopoietin receptor (MPL) gene is a critical regulator of hematopoiesis, and any alterations in its structure or function can result in a range of hematological disorders. Non-synonymous single nucleotide polymorphisms (nsSNPs) in MPL have the potential to disrupt normal protein function, prompting our investigation into the most deleterious MPL SNPs and the associated structural changes affecting protein-protein interactions. We employed a comprehensive suite of bioinformatics tools, including PredictSNP, InterPro, ConSurf, I-Mutant2.0, MUpro, Musitedeep, Project HOPE, STRING, RegulomeDB, Mutpred2, CScape, and CScape Somatic, to analyze 635 nsSNPs within the MPL gene. Among the analyzed nsSNPs, PredictSNP identified 28 as significantly pathogenic, revealing three critical functional domains within MPL. Ten of these nsSNPs exhibited high conservation scores, indicating potential effects on protein structure and function, while 14 were found to compromise MPL protein stability. Although the most harmful nsSNPs did not directly impact post-translational modification sites, 13 had the capacity to substantially alter the protein's physicochemical properties. Some mutations posed a risk to vital protein-protein interactions crucial for hematological functions, and three non-coding region nsSNPs displayed significant regulatory potential with potential implications for hematopoiesis. Furthermore, 13 out of 21 nsSNPs evaluated were classified as high-risk pathogenic variants by Mutpred2. Notably, amino acid alterations such as C291S, T293N, D295G, and W435C, while impactful on protein stability and function, were deemed non-oncogenic "passenger" mutations. Our study underscores the substantial impact of missense nsSNPs on MPL protein structure and function. Given MPL's central role in hematopoiesis, these mutations can significantly disrupt hematological processes, potentially leading to a variety of disorders. The identified high-risk pathogenic nsSNPs may hold promise as potential biomarkers or therapeutic targets for hematological diseases. This research lays the foundation for future investigations into the MPL gene's role in the realm of hematological health and diseases.

RMTLysPTM: recognizing multiple types of lysine PTM sites by deep analysis on sequences.

Post-translational modification (PTM) occurs after a protein is translated from ribonucleic acid. It is an important living creature life phenomenon because it is implicated in almost all cellular processes. Identification of PTM sites from a given protein sequence is a hot topic in bioinformatics. Lots of computational methods have been proposed, and they provide good performance. However, most previous methods can only tackle one PTM type. Few methods consider multiple PTM types. In this study, a multi-label classification model, named RMTLysPTM, was developed to recognize four types of lysine (K) PTM sites, including acetylation, crotonylation, methylation and succinylation. The surrounding sites of a lysine site were selected to constitute a peptide segment, representing the lysine at the center. Deep analysis was conducted to count the distribution of 2-residues with fixed location across the four types of lysine PTM sites. By aggregating the distribution information of 2-residues in one peptide segment, the peptide segment was encoded by informative features. Furthermore, a prediction engine that can precisely capture the traits of the above representations was designed to recognize the types of lysine PTM sites. The cross-validation results on two datasets (Qiu and CPLM training datasets) suggested that the model had extremely high performance and RMTLysPTM had strong generalization ability by testing it on protein Q16778 and CPLM testing datasets. The model was found to be generally superior to all previous models and those using popular methods and features. A web server was set up for RMTLysPTM, and it can be accessed at http://119.3.127.138/.

Detection of the Arabidopsis Proteome and Its Post-translational Modifications and the Nature of the Unobserved (Dark) Proteome in PeptideAtlas.

This study describes a new release of the Arabidopsis thaliana PeptideAtlas proteomics resource (build 2023-10) providing protein sequence coverage, matched mass spectrometry (MS) spectra, selected post-translational modifications (PTMs), and metadata. 70 million MS/MS spectra were matched to the Araport11 annotation, identifying ∼0.6 million unique peptides and 18,267 proteins at the highest confidence level and 3396 lower confidence proteins, together representing 78.6% of the predicted proteome. Additional identified proteins not predicted in Araport11 should be considered for the next Arabidopsis genome annotation. This release identified 5198 phosphorylated proteins, 668 ubiquitinated proteins, 3050 N-terminally acetylated proteins, and 864 lysine-acetylated proteins and mapped their PTM sites. MS support was lacking for 21.4% (5896 proteins) of the predicted Araport11 proteome: the "dark" proteome. This dark proteome is highly enriched for E3 ligases, transcription factors, and for certain (e.g., CLE, IDA, PSY) but not other (e.g., THIONIN, CAP) signaling peptides families. A machine learning model trained on RNA expression data and protein properties predicts the probability that proteins will be detected. The model aids in discovery of proteins with short half-life (e.g., SIG1,3 and ERF-VII TFs) and for developing strategies to identify the missing proteins. PeptideAtlas is linked to TAIR, tracks in JBrowse, and several other community proteomics resources.

Understanding the impact of structural modifications at the NNAT gene’s post-translational acetylation site: in silico approach for predicting its drug-interaction role in anorexia nervosa

PurposeAnorexia nervosa (AN) is a neuropsychological public health concern with a socially disabling routine and affects a person’s healthy relationship with food. The role of the NNAT (Neuronatin) gene in AN is well established. The impact of mutation at the protein’s post-translational modification (PTM) site has been exclusively associated with the worsening of the protein’s biochemical dynamics.MethodsTo understand the relationship between genotype and phenotype, it is essential to investigate the appropriate molecular stability of protein required for proper biological functioning. In this regard, we investigated the PTM-acetylation site of the NNAT gene in terms of 19 other specific amino acid probabilities in place of wild type (WT) through various in silico algorithms. Based on the highest pathogenic impact computed through the consensus classifier tool, we generated 3 residue-specific (K59D, P, W) structurally modified 3D models of NNAT. These models were further tested through the AutoDock Vina tool to compute the molecular drug binding affinities and inhibition constant (Ki) of structural variants and WT 3D models.ResultsWith trained in silico machine learning algorithms and consensus classifier; the three structural modifications (K59D, P, W), which were also the most deleterious substitution at the acetylation site of the NNAT gene, showed the highest structural destabilization and decreased molecular flexibility. The validation and quality assessment of the 3D model of these structural modifications and WT were performed. They were further docked with drugs used to manage AN, it was found that the ΔGbind (kcal/mol) values and the inhibition constants (Ki) were relatively lower in structurally modified models as compared to WT.ConclusionWe concluded that any future structural variation(s) at the PTM-acetylation site of the NNAT gene due to possible mutational consequences, will serve as a basis to explore its relationship with the propensity of developing AN.Level of evidenceNo level of evidence—open access bioinformatics research.