Biophysical reviews最新文献_第4页

New frontiers in applied biophysics: advancing drug discovery using single-molecule microscopy. 应用生物物理学的新领域：利用单分子显微镜推进药物发现。

IF 3.7

Biophysical reviews Pub Date : 2026-02-11 eCollection Date: 2025-12-01 DOI: 10.1007/s12551-025-01396-6

Francis Stabile, Cynthia Shaheen, Sabrina Leslie

{"title":"New frontiers in applied biophysics: advancing drug discovery using single-molecule microscopy.","authors":"Francis Stabile, Cynthia Shaheen, Sabrina Leslie","doi":"10.1007/s12551-025-01396-6","DOIUrl":"https://doi.org/10.1007/s12551-025-01396-6","url":null,"abstract":"Abstract: Since the last event of a drug interacting with its target occurs one molecule at a time, it stands to reason that the ability to observe the structures, time courses, and interactions of individual molecules will be important to optimizing drug properties. While bulk measurements provide ensemble-average properties of molecules, important information is often obscured from view. Recently, single-molecule methods have emerged in the field of drug discovery and development to fill in these gaps. Benefits of single-molecule resolution include reduced sample consumption, higher detection sensitivity, and enabling direct visualization of multi-step molecular interactions. In this review, we attempt to bridge the gap between the fields of biophysics and drug discovery to increase the interaction between these fields and drive progress together. First, we give a brief overview of the drug discovery process, which is intended for the biophysics community. Then, we review a series of single-molecule techniques, including both well-established and newly emerging technologies, highlighting key drug discovery insights and possible future applications of each technique. Looking forward, we are inspired to see the advent and application of single-molecule methods and biophysical approaches to drive real-world impacts in drug discovery by providing crucial and complementary information to bulk measurements. Looking ahead, we are excited about the widespread impact that bringing the fields of biophysics and drug discovery together will have on myriad classes of emerging medicines and energizing the required research.Graphical abstract: ","PeriodicalId":9094,"journal":{"name":"Biophysical reviews","volume":"17 6","pages":"1807-1833"},"PeriodicalIF":3.7,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12957680/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147364011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Voltage-dependent potassium channel regulatory subunits in the immune system. 免疫系统中电压依赖性钾通道调节亚基。

IF 5

Biophysical reviews Pub Date : 2026-02-11 eCollection Date: 2026-02-01 DOI: 10.1007/s12551-026-01412-3

Magalí Colomer-Molera, Silvia Cassinelli, María Navarro-Pérez, Antonio Felipe

{"title":"Voltage-dependent potassium channel regulatory subunits in the immune system.","authors":"Magalí Colomer-Molera, Silvia Cassinelli, María Navarro-Pérez, Antonio Felipe","doi":"10.1007/s12551-026-01412-3","DOIUrl":"10.1007/s12551-026-01412-3","url":null,"abstract":"The immune system depends on ion channels to control activation and maintain cellular homeostasis. The role of voltage-dependent potassium channels (Kv) in immune cells has been well studied in recent decades, with a special interest in the role of Kv1.3 in cell physiology and its implications in autoimmune diseases. However, native K+ currents in leukocytes result not only from the assembly of pore-forming α-subunits but are also shaped by regulatory β-subunits that fine-tune gating, trafficking, and pharmacology. Immune cells express members of the Kvβ, KCNE, and KChIP families, but the contribution of these regulatory subunits to immune physiology remains largely underexplored. In this review, we synthesize evidence for regulatory subunit expression and function in leukocytes, focusing on how these partners modify Kv channel behavior and downstream signaling. We highlight Kv1.3-Kvβ2.1-KCNE4 as a promising immunoregulatory complex, and we discuss the role of KChIPs in shaping gene expression as well as a Kv regulatory subunit. Despite gaps in the expression of regulatory subunits in immune cells, increasing evidence highlights the importance of further studies addressing the role of Kvβ-subunits in the immune context. Understanding how Kv channels are regulated in leukocytes could lead to new ways to control immune responses and develop new targeted therapies.","PeriodicalId":9094,"journal":{"name":"Biophysical reviews","volume":"18 1","pages":"155-168"},"PeriodicalIF":5.0,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13031570/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147571992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ion transport in biological ion channels beyond classical electrostatics. Nanoscale confinement, non-linear concentration patterns and interfacial effects. 超越经典静电学的生物离子通道中的离子传输。纳米尺度约束，非线性浓度模式和界面效应。

IF 5

Biophysical reviews Pub Date : 2026-02-10 eCollection Date: 2026-02-01 DOI: 10.1007/s12551-026-01413-2

María Queralt-Martín, Laidy M Alvero-González, D Aurora Perini, Elena García-Giménez, Antonio Alcaraz

{"title":"Ion transport in biological ion channels beyond classical electrostatics. Nanoscale confinement, non-linear concentration patterns and interfacial effects.","authors":"María Queralt-Martín, Laidy M Alvero-González, D Aurora Perini, Elena García-Giménez, Antonio Alcaraz","doi":"10.1007/s12551-026-01413-2","DOIUrl":"10.1007/s12551-026-01413-2","url":null,"abstract":"Membrane transport has been the subject of intense investigation during decades in diverse scientific disciplines like physical chemistry, biophysics, and electrochemistry. While simplified models derived from continuous electrostatics generally hold, nanometer-sized channels often exhibit unexpected behaviors that stem from a variety of factors including the molecular nature of the solvent or the charge-charge correlations involving both the permeating ions and fixed charges within the membrane-pore system. In this short review, we summarize recent work focusing on two different salt concentration regimes with behaviors that contradict classical models. First, at low concentrations, critical interfacial effects such as access resistance occur involving a non-trivial interplay between membrane and protein charges. Second, in concentrated solutions, many ion transport properties show non-monotonic concentration patterns compatible with underscreening. Understanding these nanoscale deviations from typical microscale behavior is essential for accurately predicting the function of biological ion channels and designing advanced, atomic-sized fluidic devices for industry.","PeriodicalId":9094,"journal":{"name":"Biophysical reviews","volume":"18 1","pages":"191-199"},"PeriodicalIF":5.0,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13031438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147572514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Advances in molecular dynamics approaches for investigating cell-penetrating peptides. 分子动力学方法研究细胞穿透肽的进展。

IF 5

Biophysical reviews Pub Date : 2026-02-10 eCollection Date: 2026-02-01 DOI: 10.1007/s12551-026-01409-y

Eric Catalina-Hernandez, Alex Peralvarez-Marin

{"title":"Advances in molecular dynamics approaches for investigating cell-penetrating peptides.","authors":"Eric Catalina-Hernandez, Alex Peralvarez-Marin","doi":"10.1007/s12551-026-01409-y","DOIUrl":"10.1007/s12551-026-01409-y","url":null,"abstract":"Membrane active peptides (MAPs) are short, cationic peptides capable of interacting with biological membranes, often altering their structure or function. Two of the most important classes of MAPs are cell-penetrating peptides (CPPs), which can translocate cellular membranes without causing cytotoxicity, and antimicrobial peptides (AMPs), peptides that can disrupt microbial membranes through pore formation or membrane lysis. Despite extensive experimental research, a comprehensive understanding of CPPs' mechanism at the molecular level remains elusive. Molecular dynamics (MD) simulations offer a powerful approach to investigate protein-lipid interactions and the dynamic behavior of peptide-membrane systems at atomic resolution. Nonetheless, capturing these complex processes through conventional MD simulations is computationally demanding. To address this, a range of enhancing sampling techniques has been developed. In this review, we discuss the MD methodologies available for studying CPPs' interactions with membranes, focusing on the techniques introduced by our group. Our aim is to provide a useful reference for future investigations into peptide-membrane interactions, ultimately advancing molecular-level insight into these biologically significant systems.","PeriodicalId":9094,"journal":{"name":"Biophysical reviews","volume":"18 1","pages":"133-154"},"PeriodicalIF":5.0,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13031446/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147572511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Modulating the myosin super-relaxed state as a therapeutic strategy for myosin light chain-linked cardiomyopathies. 调节肌凝蛋白超放松状态作为肌凝蛋白轻链型心肌病的治疗策略。

IF 5

Biophysical reviews Pub Date : 2026-02-09 eCollection Date: 2026-06-01 DOI: 10.1007/s12551-026-01420-3

Danuta Szczesna-Cordary

{"title":"Modulating the myosin super-relaxed state as a therapeutic strategy for myosin light chain-linked cardiomyopathies.","authors":"Danuta Szczesna-Cordary","doi":"10.1007/s12551-026-01420-3","DOIUrl":"https://doi.org/10.1007/s12551-026-01420-3","url":null,"abstract":"In this review, we summarize a series of studies focused on cardiac myosin light chains and hereditary human mutations that cause hypertrophic (HCM), restrictive (RCM), or dilated (DCM) cardiomyopathy. In the heart, myosin serves as the molecular motor that converts the chemical energy of ATP hydrolysis into mechanical force, enabling cardiac contraction and blood pumping. Both myosin light chains, the regulatory (RLC) and essential (ELC), play critical roles in supporting and fine-tuning myosin motor function. Special emphasis is placed on the myosin super-relaxed (SRX) state, first described by Roger Cooke and colleagues more than 15 years ago. During diastole and muscle relaxation, myosin heads dynamically transition between two energetic states: the SRX state, which minimizes ATP consumption and preserves energy, and the disordered relaxed (DRX) state, in which myosin heads are more available for actin interaction but exhibit higher ATP turnover. To elucidate mechanisms underlying mutation-dependent pathological cardiac remodeling, we assessed the relative occupancy of myosin heads between the SRX and DRX states in skinned cardiac fibers from mouse models of HCM, RCM, and DCM using single-nucleotide turnover assays developed by the Cooke laboratory. Collectively, these studies demonstrate that mutation-induced alterations in myosin energetic states and dysregulation of the SRX:DRX balance constitute a central mechanism driving the distinct clinical and functional phenotypes observed in human cardiomyopathies caused by mutations in myosin RLC and ELC.","PeriodicalId":9094,"journal":{"name":"Biophysical reviews","volume":"18 3","pages":"641-648"},"PeriodicalIF":5.0,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13486449/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148788133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Living at the border: biophysical gateways into membrane protein insertion and folding. 生活在边界：进入膜蛋白插入和折叠的生物物理通道。

IF 5

Biophysical reviews Pub Date : 2026-02-04 eCollection Date: 2026-02-01 DOI: 10.1007/s12551-026-01408-z

Brayan Grau, Ismael Mingarro

{"title":"Living at the border: biophysical gateways into membrane protein insertion and folding.","authors":"Brayan Grau, Ismael Mingarro","doi":"10.1007/s12551-026-01408-z","DOIUrl":"10.1007/s12551-026-01408-z","url":null,"abstract":"Membrane proteins inhabit a uniquely heterogeneous environment in which folding, insertion, and assembly are inseparably coupled to the physical properties of lipid bilayers. Despite their central biological relevance, the principles governing membrane protein folding are less well defined than those for soluble proteins due to the energetic complexity of transferring polypeptide chains across, into, or along membranes. This review examines the biophysical determinants that shape the early stages of α-helical membrane protein folding, emphasizing the membrane-water interface as a critical energetic gateway. We trace the historical development of hydrophobic scales, from early solvent-based peptide measurements to membrane-translocon-derived scales, highlighting how successive refinement has revealed distinct energetic preferences for aqueous, interfacial, and fully inserted states. Building on this framework, we discuss how co-translational folding within the ribosome exit tunnel and the ribosome-translocon complex constrains secondary structure formation and modulates the final behavior of the polypeptide segment. We further analyze the contributions of intrahelical and interhelical interactions, lipid-protein coupling, and bilayer adaptability in stabilizing transmembrane helices and promoting higher-order assembly. Finally, we integrate these concepts into a unified view in which membrane protein biogenesis emerges as a continuous energy-driven process where sequence-encoded information, molecular machinery, and membrane physics converge to ensure faithful folding, topogenesis, and quality control.","PeriodicalId":9094,"journal":{"name":"Biophysical reviews","volume":"18 1","pages":"121-132"},"PeriodicalIF":5.0,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13031457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147572552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Using atomic force microscopy for physical virology: touching and manipulating single virus particles. 使用原子力显微镜进行物理病毒学：触摸和操纵单个病毒颗粒。

IF 5

Biophysical reviews Pub Date : 2026-01-30 eCollection Date: 2026-02-01 DOI: 10.1007/s12551-026-01407-0

Alejandro Díez-Martínez, Klara Strobl, A Cámara-Ballesteros, R Delgado-Buscalioni, Pedro José de Pablo

{"title":"Using atomic force microscopy for physical virology: touching and manipulating single virus particles.","authors":"Alejandro Díez-Martínez, Klara Strobl, A Cámara-Ballesteros, R Delgado-Buscalioni, Pedro José de Pablo","doi":"10.1007/s12551-026-01407-0","DOIUrl":"10.1007/s12551-026-01407-0","url":null,"abstract":"Atomic force microscopy (AFM) employs a nanometer-scale tip mounted on a microcantilever to scan surfaces where virus particles have been captured. Beyond generating high-resolution images of individual virions in liquid, AFM offers unique capabilities: manipulation of single particles, investigation of their biomechanical properties, and real-time observation of assembly and disassembly processes, including genome release. This chapter begins by outlining fundamental aspects of virus adsorption and imaging, highlighting, among other factors, the influence of tip-convolution artifacts. These principles are applied to reveal the adsorption behavior of the TGEV coronavirus on surfaces. Subsequent sections detail approaches for probing TMV's mechanical properties through single-indentation experiments and mechanical fatigue protocols. In this section, the mechanical fatigue approach is also discussed when used on 2D arrays of viral coat proteins. The review also discusses how these mechanical techniques can trigger genome release in minute virus of mice (MVM), a process that can alternatively be induced by temperature, as happens in bacteriophage T7. Finally, the chapter illustrates how AFM can serve as a nanomanipulation tool to move individual viruses across surfaces and estimate their adhesion strength.","PeriodicalId":9094,"journal":{"name":"Biophysical reviews","volume":"18 1","pages":"95-108"},"PeriodicalIF":5.0,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13031453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147571846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Predicting and monitoring treatment response via 1-H NMR metabolomics of plasma, serum, and urine. 通过血浆、血清和尿液的1-氢核磁共振代谢组学预测和监测治疗反应。

IF 3.7

Biophysical reviews Pub Date : 2026-01-27 eCollection Date: 2025-12-01 DOI: 10.1007/s12551-026-01405-2

Shashikant Kotwal, Jong Wook Shin, Tedros Bezabeh

{"title":"Predicting and monitoring treatment response via 1-H NMR metabolomics of plasma, serum, and urine.","authors":"Shashikant Kotwal, Jong Wook Shin, Tedros Bezabeh","doi":"10.1007/s12551-026-01405-2","DOIUrl":"https://doi.org/10.1007/s12551-026-01405-2","url":null,"abstract":"The field of metabolomics is witnessing a rapid growth in its applications. Applications related to biomarker discovery for the purposes of disease diagnosis constitute a major part of that growth. Of equal interest is the ability to predict and assess treatment responses in various diseases. Obtaining such information before the start of treatment or early on during the treatment, without the need to perform invasive biopsy procedures, would greatly improve patient care and management. This would allow the physician to find alternative treatments and/or modify or stop ongoing treatment when no-response or adverse effects are observed, thereby sparing the patient from continuing with unnecessary and/or toxic treatments. The latter is especially important in the treatment of many cancers. The current literature on the applications of metabolomics to the monitoring of treatment is limited. Here we compile NMR-based metabolomics studies on plasma, serum, and urine geared towards such applications focusing on cancer, hepatotoxicity, neurological disorders, transplants (renal and liver), and sepsis. We discuss the challenges faced in these applications along with approaches to address these difficulties. Finally, insight into the future of this approach and how it can move closer to clinical utility is shared.","PeriodicalId":9094,"journal":{"name":"Biophysical reviews","volume":"17 6","pages":"1781-1794"},"PeriodicalIF":3.7,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12957675/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147364021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Minor groove tetrads: a potent and versatile capping interaction for i-motif structures. 小凹槽四分体：i-motif结构的有效和通用的封盖相互作用。

IF 5

Biophysical reviews Pub Date : 2026-01-22 eCollection Date: 2026-02-01 DOI: 10.1007/s12551-026-01406-1

Miguel Garavís, Bartomeu Mir, Israel Serrano-Chacón, Cristina Cabrero, Cristina Ugedo, Irene Gómez-Pinto, Núria Escaja, Carlos González

{"title":"Minor groove tetrads: a potent and versatile capping interaction for i-motif structures.","authors":"Miguel Garavís, Bartomeu Mir, Israel Serrano-Chacón, Cristina Cabrero, Cristina Ugedo, Irene Gómez-Pinto, Núria Escaja, Carlos González","doi":"10.1007/s12551-026-01406-1","DOIUrl":"10.1007/s12551-026-01406-1","url":null,"abstract":"Minor groove tetrads (MGTs) have emerged as powerful structural elements capable of enhancing the stability and versatility of i-motif DNA structures. These non-canonical tetrads, formed by the minor groove association of two Watson-Crick or mismatched base pairs, act as capping platforms that reinforce hemiprotonated C:C⁺ stacks, enabling i-motif folding even at neutral pH. The resulting MGT-containing i-motifs (MGTiMs) display exceptional thermal and pH stability, tunable topology, and remarkable structural plasticity. Recent studies have revealed that MGTiMs can form compact architectures with only two C:C⁺ pairs, undergo reversible pH-dependent conformational transitions, and integrate seamlessly into duplex junctions without distorting B-DNA geometry. These insights may add new principles for rational i-motif engineering, guiding the design of predictable, homogeneous, and responsive DNA nanostructures. Furthermore, the synergy between MGT stabilization and chemical modifications, such as 2'-fluoro substitutions or fluorescent cytosine analogues, offers powerful tools for real-time structural monitoring and in-cell imaging. Beyond fundamental structural biology, MGTiMs hold strong potential for applications in biosensing, nanotechnology, and synthetic biology, providing programmable molecular systems that combine biocompatibility, robustness, and responsiveness to physiological stimuli.","PeriodicalId":9094,"journal":{"name":"Biophysical reviews","volume":"18 1","pages":"109-119"},"PeriodicalIF":5.0,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13031437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147572489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

AGGRESCAN and its evolution: A two-decade perspective on protein aggregation prediction. 侵略者及其进化：二十年来蛋白质聚集预测的观点。

IF 5

Biophysical reviews Pub Date : 2026-01-19 eCollection Date: 2026-02-01 DOI: 10.1007/s12551-025-01404-9

Giulia Pesce, Oriol Solé, Oriol Bárcenas, Salvador Ventura

{"title":"AGGRESCAN and its evolution: A two-decade perspective on protein aggregation prediction.","authors":"Giulia Pesce, Oriol Solé, Oriol Bárcenas, Salvador Ventura","doi":"10.1007/s12551-025-01404-9","DOIUrl":"10.1007/s12551-025-01404-9","url":null,"abstract":"Protein aggregation is a widespread phenomenon with profound biological, biomedical, and biotechnological implications. In human disease, aberrant protein self-assembly is a hallmark of numerous neurodegenerative disorders, whereas in the biopharmaceutical industry, aggregation complicates the production, stability, and formulation of therapeutic proteins. The Aggrescan platform was one of the first empirically based tools designed to predict aggregation-prone regions (APRs) within protein sequences. It has since expanded to incorporate three-dimensional structural contexts and environmental conditions. This review provides a comprehensive overview of the development, application, and impact of the Aggrescan family of tools, which includes AGGRESCAN, Aggrescan3D, and the recent Aggrescan4D. We examine the algorithmic foundations, empirical validation, and key use cases spanning fields from biotechnology to biomedical research. Additionally, we describe how the recent integration of AlphaFold models has enabled proteome-scale exploration of aggregation determinants. This review highlights how Aggrescan has evolved alongside with advances in the field, becoming a reliable and accessible tool for studying and redesigning protein aggregation.","PeriodicalId":9094,"journal":{"name":"Biophysical reviews","volume":"18 1","pages":"83-94"},"PeriodicalIF":5.0,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13031676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147572486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0