Article
Chemistry, Physical
Mohd Younus Bhat, Irfan Mir, Laishram Rajendrakumar Singh, Mahboobul Hussain, Tanveer Ali Dar
Summary: Intrinsically disordered proteins (IDPs) play important roles in cellular processes and disease processes, and trehalose affects the structural-functional elasticity of IDPs.
JOURNAL OF MOLECULAR LIQUIDS
(2023)
Article
Biochemistry & Molecular Biology
Vladimir N. Uversky, Prakash Kulkarni
Summary: Intrinsic disorder has revolutionized modern protein science, challenging traditional lock-and-key model and paving the way for a new understanding of protein structure-function relationship. The discovery of protein intrinsic disorder phenomenon was a gradual process, where previous discoveries laid the foundation for a paradigm shift in the field.
BIOPHYSICAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Thinh D. N. Luong, Suhani Nagpal, Mourad Sadqi, Victor Munoz
Summary: This article introduces a method called "Molecular LEGO" that allows for the dissection of conformational landscapes of unbound intrinsically disordered proteins (IDPs) and provides insights into the functional mechanisms of these proteins. The method was applied to the protein NCBD and revealed specific energetic biases and conformational rheostatic behavior in NCBD's folding landscape, which are likely crucial for its function as a transcriptional coactivator.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Biochemistry & Molecular Biology
Tanuj Handa, Debanjan Kundu, Vikash Kumar Dubey
Summary: The importance of protein structure in performing biological functions optimally is being challenged by the emergence of intrinsically disordered proteins (IDPs) and intrinsically disordered protein regions (IDPRs). Understanding the evolutionary and functional significance of these proteins is crucial in studying various organisms. This review highlights the importance of IDPs in the physiology of specific organisms and establishes a positive correlation between IDPs and their relevance in human health and future medicine. Extensive research on IDPs and IDPRs will greatly contribute to expanding the field of structural biology, aiding in the comprehension of protein folding, misfolding, associated diseases, and drug design.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Biochemistry & Molecular Biology
San Hadzi, Jurij Lah
Summary: Intrinsically disordered proteins (IDPs) are common in eukaryotic proteomes and can acquire defined conformations upon binding globular targets. The folding penalty of IDPs in alpha-helical binding motifs has been estimated to be around +2.0 kcal/mol, with a range of 0.7 to 3.5 kcal/mol. Pre-folding and target-bound IDP dynamics reduce the folding cost by approximately half. Understanding the role of folding penalty in IDP-target interactions and estimating this quantity can aid in the design of inhibitors for IDP-target interactions.
Article
Biochemistry & Molecular Biology
Jaime Santos, Irantzu Pallares, Valentin Iglesias, Salvador Ventura
Summary: The prevalence of cryptic amyloidogenic regions (CARs) of polar nature in intrinsically disordered regions (IDRs) has been explored. CARs are associated with protein function and interactions, but also carry a risk of malfunction. The existence of ancestral CARs may have evolved into functional interacting regions, playing a significant role in protein evolution at the origins of life.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Review
Biochemistry & Molecular Biology
Owen Michael Morris, James Hilary Torpey, Rivka Leah Isaacson
Summary: This review evaluates the anatomy of intrinsically disordered proteins (IDPs) and how their intrinsic properties allow for diversity and different modes of interaction. It also provides a detailed overview of the types of disordered domains and the kinetic and thermodynamic principles governing their formation, with reference to a recent example.
Article
Biochemistry & Molecular Biology
Jaka Kragelj, Rania Dumarieh, Yiling Xiao, Kendra K. K. Frederick
Summary: Frozen proteins at cryogenic temperatures can provide detailed conformational restraints for DNP MAS NMR studies. Using peak shapes, conformational features of individual conformers in the ensemble can be assigned through simulation. This has important implications for studying proteins with intrinsically disordered regions in living cells.
Article
Geriatrics & Gerontology
Akshatha Ganne, Meenakshisundaram Balasubramaniam, Srinivas Ayyadevara, Robert J. Shmookler Reis
Summary: Protein structure is determined by amino acid sequence and post-translational modifications. Non-structured proteins, known as intrinsically disordered proteins (IDPs), are overrepresented in protein aggregates associated with neurodegenerative diseases. Machine learning models can predict the properties determining the enrichment of IDPs in neuropathic aggregates.
FRONTIERS IN AGING NEUROSCIENCE
(2022)
Review
Biochemistry & Molecular Biology
Rakesh Trivedi, Hampapathalu Adimurthy Nagarajaram
Summary: This review discusses different aspects of disordered proteins and protein regions, as well as the experimental and computational methods used to characterize them. Additionally, the role of disordered proteins in diseases and their potential as drug targets are explored.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Maurizio Brunori, Stefano Gianni
Summary: The study of the mechanisms behind how proteins achieve their functional conformations has been a key issue in molecular biosciences for the past 60 years. However, there are still debated issues and open problems regarding certain aspects of this fundamental problem. This article attempts to propose a personal account on key topics in the field, ranging from the relationship between misfolding and diseases to the significance of protein disorder. Lastly, recent advances in predicting protein structures from amino acid sequences are briefly described.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Guy Jacoby, Merav Segal Asher, Tamara Ehm, Inbal Abutbul Ionita, Hila Shinar, Salome Azoulay-Ginsburg, Ido Zemach, Gil Koren, Dganit Danino, Michael M. Kozlov, Roey J. Amir, Roy Beck
Summary: This study introduces a new type of peptide amphiphiles, intrinsically disordered peptide amphiphiles (IDPA), that exhibit a sharp pH-induced micellar phase-transition. The shape transition can serve as a mechanism for the design of cargo hold-and-release applications, demonstrating the potential of tailoring interactions between disordered peptides for various stimuli-responsive biomedical applications.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Multidisciplinary
Sanchita Sanchaya Dey, Rahul Chakraborty, Bhupesh Taneja
Summary: PacC is a key transcriptional regulator of Trichophyton rubrum, a human pathogenic fungus. The C-terminal inhibitory tail of PacC plays a crucial role in maintaining its inactive state at acidic pH and undergoes conformational changes for its activation at alkaline pH. The tail exhibits properties similar to intrinsically disordered proteins and may play a significant role in modulating the pH-dependent transcriptional activation of PacC.
Review
Biochemistry & Molecular Biology
Kiersten M. Ruff, Rohit Pappu
Summary: Accurate predictions of protein structures using AlphaFold have made significant progress. Most protein sequences in the human proteome have been structurally annotated, with over 30% of regions being disordered.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Review
Chemistry, Multidisciplinary
Pablo G. Argudo, Juan J. Giner-Casares
Summary: Proteins and peptide fragments play a crucial role in self-assembly for nanostructures, with intrinsically disordered proteins and protein regions showing significant biological activity. Experimental techniques and computational modeling procedures are used for characterization, leading to a wide variety of nanostructures and promising performance in biotechnological applications. Exciting possibilities for IDPs and IDRs in nanotechnology with relevant biological applications are demonstrated.
NANOSCALE ADVANCES
(2021)
Article
Biochemistry & Molecular Biology
Anas Shamsi, Taj Mohammad, Saleha Anwar, Khalida Nasreen, Md Imtaiyaz Hassan, Faizan Ahmad, Asimul Islam
Summary: This study investigated the binding of alpha-crystallin and PEG-400 using various spectroscopic techniques and molecular modeling. The results suggest a strong binding between alpha-crystallin and PEG-400, driven by van der Waals forces and hydrogen bonding. Molecular docking further confirmed the binding site of PEG-400 in alpha-crystallin.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Biochemistry & Molecular Biology
Abdullah Naiyer, Bushra Khan, Asimul Islam, Md Imtaiyaz Hassan, Monica Sundd, Faizan Ahmad
Summary: The structure, stability, and dynamics properties of horse cytochrome c and its M80G mutant have been investigated. The effect of the M80G mutation on the protein's structure and stability was examined, and the dynamic behavior of the WT cyt c and its M80G mutant was measured. The results showed that the mutation caused partial loss of structure but slightly increased overall stability, and the mutant had increased stability and flexibility compared to the wild-type.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Biochemistry & Molecular Biology
Neha Raina, Md. Imtaiyaz Hassan, Faizan Ahmad, Asimul Islam, Amit Kumar Singh
Summary: Crowding and confinement in macromolecular environments can affect protein stability through a balance of hard-core repulsion and chemical interactions. Past studies have shown the impact of PEG on proteins, with destabilizing interactions potentially caused by excluded volume effects or changes in solvent properties. Charge-charge and hydrophobic interactions play a significant role in destabilizing protein interactions, particularly in the presence of crowding agents like proteins.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Editorial Material
Dermatology
Gagan Chhabra, Nihal Ahmad
Summary: This preclinical study highlights the detrimental effects of sustained BRAF inhibitor treatment on BRAF/NRAS mutant melanoma cells, as it enhances the expression of genes involved in tumor growth and metastasis. It suggests caution in the use of BRAF inhibitors for patients with NRAS-driven melanoma.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Rashid Waseem, Anas Shamsi, Taj Mohammad, Md. Imtaiyaz Hassan, Syed Naqui Kazim, Anis Ahmad Chaudhary, Hassan Ahmed Rudayni, Mohammed Al-Zharani, Faizan Ahmad, Asimul Islam
Summary: A sedentary lifestyle increases the risk of various diseases, while physical exercise reduces these risks. Irisin, a hormone induced by exercise, plays a crucial role in connecting muscles and other tissues and has beneficial effects on fat cells, metabolic processes, bone metabolism, and the nervous system. It also has a role in cancer development and may act via specific integrin receptors. Past research has identified irisin as a potential therapeutic agent for metabolic-related and other diseases.
Article
Chemistry, Multidisciplinary
Wahiduzzaman, Vijay Kumar, Farah Anjum, Alaa Shafie, Abdelbaset Mohamed Elasbali, Asimul Islam, Faizan Ahmad, Md Imtaiyaz Hassan
Summary: The study identified four peptides derived from the SOD1 gene that may be involved in fibril formation in ALS, with the C-terminal peptides playing a central role in amyloid formation. The mutations in the peptide (147)GVIGIAQ(153) increased the fibril-forming propensity and altered the steric zipper's packing, suggesting a potential involvement in the structural core of SOD1 aggregation observed in vivo.
Article
Dermatology
Gagan Chhabra, Chandra K. Singh, Glorimar Guzman-Perez, Mary A. Ndiaye, Kenneth A. Iczkowski, Nihal Ahmad
Summary: In this study, the antimelanoma efficacy of 4'-bromo-resveratrol (4'-BR) was demonstrated in a mouse model of metastatic melanoma. The treatment significantly reduced the size and volume of primary melanoma tumors, as well as lung metastasis. Mechanistic studies showed modulation in markers of proliferation, survival, and melanoma progression. The treatment also downregulated genes related to metastasis promotion, chemokine/cytokine regulation, and immune functions.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2022)
Article
Chemistry, Physical
Rashid Waseem, Anas Shamsi, Mohd Shahbaz, Tanzeel Khan, Syed Naqui Kazim, Faizan Ahmad, Md Imtaiyaz Hassan, Asimul Islam
Summary: The study investigated the structural and conformational changes of irisin at different pH levels. Findings show that irisin is more stable at acidic pH, with maximum stability observed at pH 4.0.
JOURNAL OF MOLECULAR STRUCTURE
(2022)
Article
Endocrinology & Metabolism
Chandra K. Singh, Ryan A. Denu, Minakshi Nihal, Maria Shabbir, Debra R. Garvey, Wei Huang, Kenneth A. Iczkowski, Nihal Ahmad
Summary: The role of PLK4 in prostate cancer and the prevalence of centrosome amplification (CA) were investigated in this study. The results showed that CA in prostate cancer is mainly caused by centriole overduplication, and PLK4 inhibition may be a potential therapeutic strategy for prostate cancer.
Letter
Dermatology
Rubab Raza, Gagan Chhabra, Muhammad Bilal, Mary A. Ndiaye, Khurram Liaqat, Shoaib Nawaz, Jean-Yves Sgro, Ivan Rayment, Wasim Ahmad, Nihal Ahmad
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2023)
Article
Oncology
Aishwarya Krishnan, Aishwarya I. Bhasker, Mithalesh K. Singh, Carlos. I. Rodriguez, Edgardo Castro Perez, Sarah Altameemi, Marcos Lares, Hamidullah Khan, Mary Ndiaye, Nihal Ahmad, Stefan M. Schieke, Vijayasaradhi Setaluri
Summary: EPAC signaling pathway plays a crucial role in the growth and survival of primary melanoma cells. Its inhibition selectively affects cell-cycle proteins and influences the progression of primary melanoma cells. EPAC also regulates glycolysis, oxidative phosphorylation, and production of mitochondrial reactive oxygen species. Loss of dependency on EPAC signaling correlates with melanoma progression, making EPAC a potential prognostic marker and therapeutic target.
MOLECULAR CANCER RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Saima Suleman, Gagan Chhabra, Rubab Raza, Arslan Hamid, Javed Anver Qureshi, Nihal Ahmad
Summary: This study assessed the association between nsSNPs of the CARD14 gene and psoriasis in a Pakistani population. The study found that two nsSNPs, rs2066965 and rs34367357, were associated with psoriasis, and that the heterozygous genotype of rs2066965 was more prevalent in patients with joint pain.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Dermatology
Bo Dong, Laura Simonson, Samantha Vold, Ethan Oldham, Lillian Barten, Nihal Ahmad, Hao Chang
Summary: This study reveals that FZD6 gene is overexpressed in multiple melanoma cell lines and human samples. Knockdown or knockout of FZD6 does not affect cell proliferation but significantly reduces the invasive ability of melanoma cells. Knockout of Fzd6 also dramatically reduces lung metastasis in the Pten/BRaf mouse model of melanoma, indicating a promoter role of FZD6 in melanoma progression.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2023)
Article
Polymer Science
Zahoor Ahmad Parray, Ahmad Abu Turab Naqvi, Ishfaq Ahmad Ahanger, Mohammad Shahid, Faizan Ahmad, Md Imtaiyaz Hassan, Asimul Islam
Summary: It is known that macromolecular crowding in the cell affects protein structure, stability, and function, but predictive studies are still relatively unexplored. This study investigated the effects of polyethylene glycol (PEG 400 Da), ethylene glycol (EG), and their mixture on the structural stability of cytochrome c (cyt c). The results showed that EG stabilizes the protein and has no significant effect on the tertiary structure, while PEG 400 destabilizes the protein structure and stability. However, EG counteracts the destabilizing effect of PEG 400. This study highlights the importance of protein folding and interactions in the crowded cellular environment.
Article
Education & Educational Research
Faizan Ahmad, Luo Zongwei, Zeeshan Ahmed, Sara Muneeb
Summary: This paper presents an empirical study on the experiences of players during brain games play, analyzing correlations among different types of experiences and identifying similarities and differences among different age groups. The observations provide insights to predict players' behavioral trends and simplify the user feedback process.
INTERACTIVE LEARNING ENVIRONMENTS
(2023)