Advances in protein chemistry and structural biology最新文献

{"title":"Accurate coarse grained models for protein association and recognition.","authors":"Agustí Emperador, Elvira Guàrdia","doi":"10.1016/bs.apcsb.2024.11.011","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2024.11.011","url":null,"abstract":"<p><p>Protein-protein interactions are fundamental to the cell function, but some of them are slow processes happening in time scales in the microsecond to millisecond range, therefore inaccessible for standard atomistic molecular dynamics (MD) simulations. A way to reduce the computational cost demanded by the simulation of long timescale phenomena is to use coarse-grained (CG) models to reduce the number of particles included in the simulation. In this Review we provide an overview of CG models for the study of protein dynamics and interactions. The majority of protein CG models have been designed to describe accurately the structure of folded, stable proteins, but recently new CG models and force fields have been designed to study disordered proteins. The difficulty of finding a force field fully transferable between stable and disordered proteins hinders the computational study of the intracellular environment in its most complex case, where protein-protein interactions occur in multiprotein systems constituted by both stable and disordered proteins. In this Review we overview several existing CG protein models, focusing on its applicability to the study of multiprotein systems including both stable and disordered proteins. We also discuss the utility of implicit solvent models, which accelerate the conformational sampling of protein solutions, to explore a broader configurational space of the system in shorter simulation times, and analyze the inaccuracies inherent to this approximation.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"145 ","pages":"1-21"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcription factors and genome biases in polyploid crops.","authors":"Raminder Kaur, Vikas Rishi","doi":"10.1016/bs.apcsb.2024.09.005","DOIUrl":"10.1016/bs.apcsb.2024.09.005","url":null,"abstract":"<p><p>Nuclear protein transcription factors (TFs) regulate all biological processes in plants and are necessary for gene regulation. The transcription of genes during plant growth and development and their response to environmental cues are regulated by TF binding to specific promoter regions in the genomic DNA. Polyploid plants with several sets of chromosomes frequently display intricate genomic biases concerning TF expression. One or more subgenomes may dominate in terms of gene expression, leading to subgenome biases or dominance. These biases can influence various aspects of the crop's biology, including its growth, development, and adaptation. Advances in genomics have speed up the improvement of many important agricultural diploid crops, yet comparable endeavours in polyploid crops have been more challenging. This challenge primarily stems from the large size and intricate nature of the complex genome in polyploid crops, along with the need for comprehensive genome assembly data for such crop varieties as bread wheat, cotton and sugarcane. Several studies have evaluated the biased/asymmetric gene expression patterns, including TFs, within the polyploid crop genomes. In many polyploid crops, not all homologues of TF genes contribute equally to the phenotype. Here, we have examined polyploid crop plants for homeolog gene expression, emphasizing TFs. It is observed that the polyploids retain many gene alleles as functional homeologs that define important features involved in stress response, sugar metabolism, and fibre formation. The possible molecular mechanism describing the structural and epigenetic basis of differential subgenomic TF expression in polyploids is discussed.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"143 ","pages":"301-321"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Navigating the landscape: A comprehensive overview of computational approaches in therapeutic antibody design and analysis.","authors":"Amar Jeet Yadav, Khushboo Bhagat, Akshit Sharma, Aditya K Padhi","doi":"10.1016/bs.apcsb.2024.10.011","DOIUrl":"10.1016/bs.apcsb.2024.10.011","url":null,"abstract":"<p><p>Immunotherapy, harnessing components like antibodies, cells, and cytokines, has become a cornerstone in treating diseases such as cancer and autoimmune disorders. Therapeutic antibodies, in particular, have transformed modern medicine, providing a targeted approach that destroys disease-causing cells while sparing healthy tissues, thereby reducing the side effects commonly associated with chemotherapy. Beyond oncology, these antibodies also hold promise in addressing chronic infections where conventional therapeutics may fall short. However, antibodies identified through in vivo or in vitro methods often require extensive engineering to enhance their therapeutic potential. This optimization process, aimed at improving affinity, specificity, and reducing immunogenicity, is both challenging and costly, often involving trade-offs between critical properties. Traditional methods of antibody development, such as hybridoma technology and display techniques, are resource-intensive and time-consuming. In contrast, computational approaches offer a faster, more efficient alternative, enabling the precise design and analysis of therapeutic antibodies. These methods include sequence and structural bioinformatics approaches, next-generation sequencing-based data mining, machine learning algorithms, systems biology, immuno-informatics, and integrative approaches. These approaches are advancing the field by providing new insights and enhancing the accuracy of antibody design and analysis. In conclusion, computational approaches are essential in the development of therapeutic antibodies, significantly improving the precision and speed of discovery, optimization, and validation. Integrating these methods with experimental approaches accelerates therapeutic antibody development, paving the way for innovative strategies and treatments for various diseases ranging from cancers to autoimmune and infectious diseases.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"144 ","pages":"33-76"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Host directed immunotherapy for chronic infections and cancer.","authors":"Rahul Tiwari, Vishal Kumar Singh, Vibhav Gautam, Sanjana Mehrotra, Rajiv Kumar","doi":"10.1016/bs.apcsb.2024.10.009","DOIUrl":"10.1016/bs.apcsb.2024.10.009","url":null,"abstract":"<p><p>Host-directed immunotherapy (HDI) is emerging as a transformative strategy in managing chronic diseases by leveraging the host's immune system to combat disease. This innovative approach has shown promise in a range of conditions, including cancer and parasitic infections. In oncology, HDI aims to enhance the body's natural immune response against cancer cells through mechanisms such as immune checkpoint inhibition, monoclonal antibodies, and cytokine therapies. These strategies are designed to boost the immune system's ability to recognize and destroy tumors, improving patient outcomes and offering alternatives to traditional cancer treatments. Similarly, in parasitic infections, HDI focuses on strengthening the host's immune defenses to control and eradicate those infections. For diseases like malaria, leishmaniasis, and Chagas disease, HDI strategies may involve adjuvants or immune modulators that amplify the body's ability to target and eliminate parasites. By optimizing immune responses and reducing reliance on conventional treatments, HDI holds the potential to revolutionize therapeutic approaches across various chronic diseases. This chapter highlights the flexibility and potential of HDI in advancing treatments, offering novel ways for improving patient care and disease management.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"144 ","pages":"355-388"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alpha-synuclein aggregation in Parkinson's disease.","authors":"Igor José Siqueira da Silva, Manuele Figueiredo da Silva, Thiago Santos de Assis Dutra, Sheila Oliveira de Souza, João Xavier de Araújo-Júnior, Ana Catarina Rezende Leite, Érica Erlanny da Silva Rodrigues, Edeildo Ferreira da Silva-Júnior","doi":"10.1016/bs.apcsb.2024.11.002","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2024.11.002","url":null,"abstract":"<p><p>Alpha-synuclein (α-Syn) aggregation is closely linked to the pathogenesis of Parkinson's disease, where misfolded monomers form toxic oligomers and amyloid fibrils, which accumulate as Lewy bodies. Several factors, such as genetic mutations, interactions with lipids and proteins such as p62 and ubiquitin, as well as, environmental conditions, e. g. the presence of toxic metals that lead to oxidative stress. Advances in understanding the molecular mechanisms of Parkinson's disease have driven the search for novel therapies, including strategies to inhibit α-Syn aggregation and reduce its cytotoxicity consequently. Natural compounds, such as Skullcapflavone II, and synthetic ones, such 4-triazole phenylamides and phenethylamides, have demonstrated to reduce α-Syn fibrillation and aggregation. This chapter discusses the most recent therapeutic strategies in the treatment of Parkinson's disease concerning the implications of α-Syn.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"146 ","pages":"35-75"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144558787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mapping the pathogenic nexus: Gene overlap and protein interaction networks in Alzheimer's and breast cancer as a precursor to protein structure prediction and analysis.","authors":"Mayank Roy Chowdhury, Vijaykumar Sudarshana Deepa, Vinoth Kumar Raja","doi":"10.1016/bs.apcsb.2024.11.007","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2024.11.007","url":null,"abstract":"<p><p>This chapter focuses on how advanced computational techniques can reveal common pathways and interactions seemingly between Alzheimer's disease (AD) and breast cancer (BC). It also highlights their roles in bridging the gap between neurodegenerative and oncogenic processes by analyzing gene networks and identifying essential genes such as GAPDH, HSP90AA1, and HSPA8, which show differential regulation in AD and BC. These genes are upregulated in AD and downregulated in BC, illustrating their involvement in both disease contexts. A significant aspect of the analysis is the role of hub-bottleneck proteins within critical pathways. These hub-bottleneck proteins, including those involved in estrogen signaling, Alzheimer's disease pathways, neurodegeneration, and cancer pathways, serve as central nodes in the PPI networks. Their positioning underscores their crucial role in mediating disease mechanisms and influencing the progression of both AD and BC. The chapter emphasizes integrating gene expression data with PPI networks to uncover these critical nodes and interactions contributing to both diseases. Using network-based analysis and transcriptomics integration tools, it provides a detailed understanding of how shared genetic markers and their interactions influence disease mechanisms. This approach enables the identification of potential biomarkers and therapeutic targets by revealing underlying molecular connections and critical pathways involving hub-bottleneck proteins. The insights gained from gene overlap and PPI networks can serve as valuable input data for future studies focused on structural analysis. By laying the groundwork for understanding shared pathways and protein interactions, the research sets the stage for more detailed structural investigations and the development of precision medicine strategies tailored to the specific molecular features of Alzheimer's and breast cancer, inspiring the development of more effective treatments.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"147 ","pages":"275-331"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145090748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"G-protein coupled receptors (GPCRs) interacts with Tau protein in Alzheimer's disease.","authors":"Subashchandrabose Chinnathambi, Gowshika Velmurugan, Vaishnavi Ananthanaraya, Madhura Chandrashekar, Nagaraj Rangappa","doi":"10.1016/bs.apcsb.2024.12.002","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2024.12.002","url":null,"abstract":"<p><p>The pathophysiological scenario of Alzheimer's disease (AD) includes the misfolding and mis-sorting of two cellular proteins: Amyloid-β as plaques and microtubule-associated protein Tau as intracellular neurofibrillary tangles (NFTs). The protein oligomers are the short-lived but, highly reactive species which mediate toxicity, synaptic loss, neurodegeneration and ultimately cognitive decline. Tau oligomers can propagate through various pathway viz. the exosomal pathway, neurotransmission, cell-to-cell junction, bulk endocytosis and receptor-mediated internalization etc. The preparation, isolation and detection of oligomers were of immense importance in the current field for designing therapeutics and diagnostics. Microglia are the prime immune cells in brain which maintain the homeostasis via synaptic surveillance and tissue-remodeling. But, the senescent microglia mediate pro-inflammation, oxidative damage and phagocytosis in diseased brain. The extracellular Tau oligomers were found to interact with microglial purinergic receptor P2Y12 which then led to microglial migration, activation and phagocytosis via various remodeled actin structure. P2Y12 receptor mediates Tau oligomers-induced microglial chemotaxis by localizing with migratory actin structures such as- filopodia, lamellipodia, podosome etc. These beneficial roles of P2Y12 in microglial chemotaxis, actin remodeling and Tau clearance can be intervened as a therapeutic target in AD.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"147 ","pages":"259-273"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145090788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural insights from neuraminidase diversity: Implications for selectivity in anti-infective and anticancer strategies.","authors":"Andrea Cannarozzi, Mariateresa Volpicella, Lorenzo Guerra, Anna De Grassi, Ciro Leonardo Pierri","doi":"10.1016/bs.apcsb.2024.10.002","DOIUrl":"10.1016/bs.apcsb.2024.10.002","url":null,"abstract":"<p><p>Neuraminidases (NAs) are glycoside hydrolase enzymes pivotal in carbohydrate metabolism, ubiquitously present in viruses, bacteria, fungi, and mammals. These enzymes catalyze the cleavage of terminal sialic acid residues from glycoproteins and glycolipids, impacting various biological processes, including pathogen infections and cancer cell proliferation. In our study, we employed advanced in silico strategies to repurpose existing drugs, aiming to provide a rapid response to health emergencies posed by multi-drug-resistant bacteria and fungi, as well as expanding the arsenal of antiviral therapies. Phylogenetic and structural superimposition analyses revealed four principal NA clusters, grouping viral, bacterial, fungal, and metazoa NAs. Comprehensive sequence and structural analyses identified three conserved binding regions across diverse species. The first binding region, observed in NAs crystallized with 23 different small molecules from viruses, fungi, bacteria, and metazoa, consists of three contact points hosting a basic RR dipeptide or RRN tripeptide, a basic/acidic R[E/D] dipeptide, and a basic/aromatic RY dipeptide involved in substrate/inhibitors binding. A second binding pocket was highlighted by comparing a group of NAs sampled from metazoa, fungi, and bacteria, crystallized in complex with 4 small molecules. The third binding pocket was proposed based on a fungal NA crystallized in complex with 1 small molecule. These identified binding pockets are proposed for being targettable by selective inhibitors of species-specific NAs, suggesting new avenues for anti-infective and anticancer strategies.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"147 ","pages":"499-533"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145090876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The cross-talk between ApoE and Tau protein in Alzheimer's disease.","authors":"Subashchandrabose Chinnathambi, Murugappan Kumarappan, Madhura Chandrashekar","doi":"10.1016/bs.apcsb.2024.08.004","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2024.08.004","url":null,"abstract":"<p><p>Alzheimer's disease is characterized by two mechanisms, one that occur extracellularly and the other occurs intracellularly. The two most important proteins are extracellular amyloid βeta (Aβ) and intracellular hyperphosphorylated Tau that are contained in senile plaques and neurofibrillary tangles respectively. AD accounts for cognitive impairment and progressive neuronal degeneration eventually, there is significant cerebral atrophy due to neuronal cell death. Initially, there is synaptic damage, synaptic loss plays a strong role in cognitive impairment in patients with AD. Also, evidence suggests that modifications in adult neurogenesis in the hippocampus plays a role in AD. It has been investigated that synaptic pathology and defective neurogenesis in AD are related to progressive accumulation of Aβ oligomers rather than fibrils. Aβ oligomer formation occurs when the APP is cleaved off and subsequently Aβ protein that is generated due to this cleavage is not cleared off by the ApoE mechanism.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"146 ","pages":"201-219"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144558794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From past to present: The evolution of immunotherapy and its modern modalities.","authors":"Surbhi Dadwal, Sarthak Dhar, Kirti Baghel, Amit Mishra, Sanjana Mehrotra, Vijay Kumar Prajapati","doi":"10.1016/bs.apcsb.2024.10.015","DOIUrl":"10.1016/bs.apcsb.2024.10.015","url":null,"abstract":"<p><p>Immunotherapy is emerging as a novel and reliable therapeutic technique for treating diseases such as autoimmunity, HIV/AIDS, allergy and cancers. This approach works by modulating the patient's immune system, activating both the innate and humoral branches to combat life-threatening diseases. The foundation of immunotherapy began with the discovery and development of \"serum therapy\" by German physiologist Emil Von Behring who received the Nobel Prize in 1901 for his contributions to the treatment of diphtheria. Around the same time, Dr. William Coley expanded the field for cancer treatment by developing the first immune based cure for sarcomas using attenuated strains of bacteria injected directly into patient's tumours. As medical science advanced, a broader understanding of the immune system and its components led to the emergence of different immunotherapeutic techniques. These include adoptive cell transfer therapy, cytokine therapy, cancer vaccines, and antibody-drug conjugates. The chapter provides a comprehensive understanding of the history and the current techniques used in immunotherapy, detailing the principles behind their mechanisms and the types of diseases tackled by each immunotherapeutic technique. By examining the journey from early discoveries to modern advancements, the chapter highlights the transformative impact of immunotherapy on medical science and patient care.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"144 ","pages":"1-32"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}