Article
Biochemical Research Methods
Long-Can Mei, Yu-Liang Wang, Feng-Xu Wu, Fan Wang, Ge-Fei Hao, Guang-Fu Yang
Summary: Protein-nucleic acid interactions, particularly involving hotspot residues, are crucial in biological processes such as transcription and drug design. Dynamic properties play a significant role in ligand binding, and HISNAPI provides insights into hotspot residue dynamics. The web server offers a valuable tool for predicting and analyzing hotspot residues on protein-nucleic acid interfaces.
BRIEFINGS IN BIOINFORMATICS
(2021)
Article
Biochemical Research Methods
Ruiming Li, Jung-Yu Lee, Jinn-Moon Yang, Tatsuya Akutsu
Summary: In this study, three graph theory-based methods are developed to predict protein hot spots by analyzing residue interaction networks. Important residues are detected by finding subgraphs with high densities. Our methods outperform existing methods on recall and F-score when evaluated on a dataset of 67 complexes from the SKEMPI database.
BMC BIOINFORMATICS
(2022)
Article
Chemistry, Medicinal
Rupeng Dai, Xueting Bao, Ying Zhang, Yan Huang, Haohao Zhu, Kundi Yang, Bo Wang, Hongmei Wen, Wei Li, Jian Liu
Summary: In this study, hot-spot residues of ERα were identified using pharmacophore modeling, molecular mechanics/generalized Born surface area (MM/GBSA), and amino-acid mutation. Hit fragments were virtually screened and linked to generate compounds, among which compound B1 showed potential for breast cancer treatment.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Biochemistry & Molecular Biology
Martin Zacharias
Summary: The rational design of protein-protein binding interfaces is crucial in generating protein assemblies with desired functions. The Match_Motif method simplifies the initial effort for designing a putative binding interface between two proteins and proposes improvements based on known protein-protein complex structures.
Review
Chemistry, Multidisciplinary
Xuefei Wang, Duan Ni, Yaqin Liu, Shaoyong Lu
Summary: This review summarizes drug design strategies for protein-protein interactions (PPIs) targeting, specifically focusing on the development of peptide-based PPI inhibitors. Examples targeting well-known PPI targets such as Bcl-2 family members, p53-MDM2, and APC-Asef are presented to illustrate detailed schemes for peptide-based PPI inhibitor development and optimization. The review provides an overview of recent advances in drug discovery targeting PPIs through peptides or peptidomimetics, offering insights into future therapeutic agent development for historically challenging PPI systems.
FRONTIERS IN CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Damla Ovek, Zeynep Abali, Melisa Ece Zeylan, Ozlem Keskin, Attila Gursoy, Nurcan Tuncbag
Summary: Proteins interact through interfaces and abnormal interactions may cause diseases. Discovering small molecules that modulate protein interactions is challenging but has high therapeutic potential. Hot spot prediction is crucial for drug design.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2022)
Article
Oncology
Jongwan Kim, Hocheol Lim, Sungho Moon, Seon Yeon Cho, Minhye Kim, Jae Hyung Park, Hyun Woo Park, Kyoung Tai No
Summary: YAP-TEAD protein-protein interaction is critical in the Hippo pathway for cancer therapy. Through hot spot analysis and FMO-based pharmacophore construction, a novel PPI inhibitor BY03 was proposed in this study, demonstrating a profitable strategy for discovering new PPI inhibitors.
Article
Engineering, Marine
Kang Wang, Yuhang Wang, Shan Gao, Bin Wang, Jinzhong Chen, Pengjun Luo
Summary: In offshore wind turbine jacket foundations, prolonged exposure to wind and wave loads can cause fatigue failure, especially at joint connections. This study investigates the distribution pattern of the hot spot stress (HSS) method in spatial tubular joints and finds that the loading conditions of neighboring braces significantly affect the distribution of HSS and the stress concentration factor (SCF). The recommended SCF calculation formulas from codes show significant discrepancies with test results, indicating the need for further research to develop suitable calculation formulas for SCFs in spatial joints.
JOURNAL OF MARINE SCIENCE AND ENGINEERING
(2023)
Article
Biology
Sang Chul Shin, Jinyoung Park, Kyung Hee Kim, Jung Min Yoon, Jinhong Cho, Byung Hak Ha, Yeonji Oh, Hyunah Choo, Eun Joo Song, Eunice EunKyeong Kim
Summary: This study investigates the functional and biochemical properties of USP47, and reveals that depleting USP47 inhibits cancer cell growth in a p53-dependent manner and that full-length USP47 has higher deubiquitinase activity. Additionally, the study provides molecular details of USP47 regulation, substrate recognition, and potential hotspots for drug discovery.
COMMUNICATIONS BIOLOGY
(2023)
Review
Chemistry, Medicinal
Bin Zhao, Ajaybabu. V. V. Pobbati, Brian. P. P. Rubin, Shaun Stauffer
Summary: The Hippo signaling pathway is involved in cell proliferation and apoptosis, and the YAP/TAZ-TEAD interaction is an important target for cancer treatment. Direct small molecule disruptors targeting TEAD interfaces 2 and 3 pose challenges in inhibitor development.
Article
Chemistry, Medicinal
Yosei Nagaoka, Prakash Parvatkar, Go Hirai, Junko Ohkanda
Summary: The study investigated the rational design of bivalent triazine-based derivatives to inhibit the activity of Cdc25B selectively, while having no effect on Cdc25A.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Biochemical Research Methods
Jianmin Wang, Yanyi Chu, Jiashun Mao, Hyeon-Nae Jeon, Haiyan Jin, Amir Zeb, Yuil Jang, Kwang-Hwi Cho, Tao Song, Kyoung Tai No
Summary: This study constructs a dataset for protein-protein interaction (PPI) targeted drug-likeness and proposes a deep molecular generative framework to generate novel drug-like molecules based on the features of seed compounds. The results show that the generated molecules have better PPI-targeted drug-likeness and drug-likeness, and the model performs comparably to other state-of-the-art molecule generation models.
BRIEFINGS IN BIOINFORMATICS
(2022)
Article
Chemistry, Multidisciplinary
Xi Yang, Dong Su, Xie Yu, Pei Zeng, Huageng Liang, Guangzu Zhang, Boxiang Song, Shenglin Jiang
Summary: The controllable nanogap structures enable strong and adjustable localized surface plasmon resonance (LSPR). A novel hierarchical plasmonic nanostructure (HPN) is created using colloidal lithography with a rotating coordinate system. The HPN increases the density of hot spots and enhances LSPR tunability and field enhancement. The hot spot engineering strategy of HPNs is demonstrated in surface-enhanced Raman spectroscopy (SERS) applications and allows single-molecule level detection and long-range mapping, providing a platform and guidance for various LSPR applications.
Article
Fisheries
Wang-Jing Liu, Yun-Shiang Chang, Kou-Chun Tseng, Meng-Hua Yu
Summary: White spot syndrome virus (WSSV) is a prominent pathogen in shrimp farming worldwide. However, there is currently no effective treatment for this virus. In this study, the antiviral properties of bovine lactoferrin (bLF) against WSSV were investigated, and it was found that bLF treatment significantly reduced shrimp mortalities caused by WSSV infection. The ability of bLF to bind to both host cells and WSSV virions suggests its potential as an anti-WSSV agent in shrimp culture, and the identified interaction proteins may play a role in WSSV infection.
DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Ashutosh Singh, Prateek Kumar, Sailu Sarvagalla, Taniya Bharadwaj, Namyashree Nayak, Mohane Selvaraj Coumar, Rajanish Giri, Neha Garg
Summary: Protein-protein interactions play important roles in both healthy and diseased states. This study identified hot spot residues within the disordered c-Myc/Myc-associated factor X interface using computational methods, and demonstrated through biophysical and cell-based experiments that small molecules can interact with these hot spots to deregulate c-Myc activity and exhibit potent anti-tumor effects against c-Myc-expressing cancer/stem cells.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Abdullahi Ibrahim Uba, Jackson Weako, Ozlem Keskin, Attila Gursoy, Kemal Yelekci
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2020)
Article
Oncology
Xinping Yang, Hui Cheng, Jianhong Chen, Ru Wang, Anthony Saleh, Han Si, Steven Lee, Emine Guven-Maiorov, Ozlem Keskin, Attila Gursoy, Ruth Nussinov, Jugao Fang, Carter Van Waes, Zhong Chen
CANCER IMMUNOLOGY RESEARCH
(2019)
Article
Multidisciplinary Sciences
John R. Pooley, Caroline A. Rivers, Michael T. Kilcooley, Susana N. Paul, Ayse Derya Cavga, Yvonne M. Kershaw, Serena Muratcioglu, Attila Gursoy, Ozlem Keskin, Stafford L. Lightman
Article
Multidisciplinary Sciences
Tunc Morova, Daniel R. McNeill, Nada Lallous, Mehmet Gonen, Kush Dalal, David M. Wilson, Attila Guersoy, Ozlem Keskin, Nathan A. Lack
NATURE COMMUNICATIONS
(2020)
Article
Biophysics
Jackson Weako, Hyunbum Jang, Ozlem Keskin, Ruth Nussinov, Attila Gursoy
Summary: This study investigates the atomic-level interaction between CaM and Akt's PHD through modeling and molecular dynamics simulations, showing that the interaction is thermodynamically stable and involves a beta-strand instead of an alpha-helix. The polar head of PIP3 weakens the CaM-PHD interaction, suggesting a release mechanism at the plasma membrane.
BIOPHYSICAL JOURNAL
(2021)
Article
Neurosciences
Hale Yapici-Eser, Yunus Emre Koroglu, Ozgur Oztop-Cakmak, Ozlem Keskin, Attila Gursoy, Yasemin Gursoy-Ozdemir
Summary: A computational analysis was conducted to investigate the molecular pathways of COVID-19 associated neuropsychiatric symptoms, revealing potential interactions between SARS-CoV-2 proteins and human proteins that could lead to delirium, psychosis, seizures, and other symptoms. Further in vivo and in vitro studies using the identified proteins may offer new targets for managing neuropsychiatric presentations.
FRONTIERS IN HUMAN NEUROSCIENCE
(2021)
Article
Chemistry, Physical
Simge Senyuz, Hyunbum Jang, Ruth Nussinov, Ozlem Keskin, Attila Gursoy
Summary: Rac1 is a key GTPase protein involved in cellular biology and diseases, with mutations like P29S and A159V associated with melanoma and head and neck cancer, respectively. These mutations activate Rac1 through different mechanisms, affecting the conformation of Switch I in GTP-bound states.
JOURNAL OF PHYSICAL CHEMISTRY B
(2021)
Article
Chemistry, Physical
Meryem Eren, Nurcan Tuncbag, Hyunbum Jang, Ruth Nussinov, Attila Gursoy, Ozlem Keskin
Summary: The study reveals that KRas4B exhibits partner-specific dynamics when interacting with different proteins, shedding light on the intricate protein-protein interactions involved in cellular signaling.
JOURNAL OF PHYSICAL CHEMISTRY B
(2021)
Article
Biochemical Research Methods
Damla Ovek, Ameer Taweel, Zeynep Abali, Ece Tezsezen, Yunus Emre Koroglu, Chung-Jung Tsai, Ruth Nussinov, Ozlem Keskin, Attila Gursoy
Summary: This web-based server provides navigation and visualization of possible interactions between SARS-CoV-2 and human host proteins. It catalogues all interactions, using an innovative interface mimicry strategy, allowing users to explore and view these interactions.
Article
Biochemistry & Molecular Biology
Damla Ovek, Zeynep Abali, Melisa Ece Zeylan, Ozlem Keskin, Attila Gursoy, Nurcan Tuncbag
Summary: Proteins interact through interfaces and abnormal interactions may cause diseases. Discovering small molecules that modulate protein interactions is challenging but has high therapeutic potential. Hot spot prediction is crucial for drug design.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Hansaim Lim, Fatma Cankara, Chung -Jung Tsai, Ozlem Keskin, Ruth Nussinov, Attila Gursoy
Summary: This review discusses recent advancements in computational methods for predicting microbial effects on human cells, with a focus on protein-protein interactions. Traditional methods, as well as more recent deep learning methods, are categorized and potential solutions to challenges in structure-based approaches are discussed. The review provides a brief guide to the current status and future directions in the field.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2022)
Article
Biochemical Research Methods
Hansaim Lim, Chung-Jung Tsai, Ozlem Keskin, Ruth Nussinov, Attila Gursoy
Summary: HMI-PRED 2.0 is a publicly available web service that predicts host-microbe protein-protein interaction using interface mimicry. It aims to be user-friendly without requiring extensive computational experience.
Article
Virology
Ebru Celik, Gulin Ozcan, Cansel Vatansever, Erxiati Paerhati, Mert A. Kuskucu, Ozlem Dogan, Sebile Guler Cekic, Onder Ergonul, Attila Gursoy, Ozlem Keskin, Fusun Can
Summary: The composition of vaginal microbiota is altered in pregnant women with COVID-19, characterized by increased alpha diversity, decreased Firmicutes and Lactobacillus, and increased Bacteroidota. Vaginal dysbiosis occurs in pregnant women infected with severe acute respiratory syndrome coronavirus-2.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Pol Picon-Pages, Monica Bosch-Morato, Laia Subirana, Francisca Rubio-Moscardo, Biuse Guivernau, Hugo Fanlo-Ucar, Melisa Ece Zeylan, Simge Senyuz, Victor Herrera-Fernandez, Ruben Vicente, Jose M. Fernandez-Fernandez, Jordi Garcia-Ojalvo, Attila Gursoy, Ozlem Keskin, Baldomero Oliva, Francesc Posas, Eulalia de Nadal, Francisco J. Munoz
Summary: Alzheimer's disease is caused by misfolded amyloid beta-peptide (Aβ) forming beta-sheets, but there are currently no treatments available to prevent it. Through a genome-wide screen in Saccharomyces cerevisiae, we identified 81 mammalian orthologue genes that enhance Aβ(1-42) toxicity and 157 that provide protection. Further studies revealed that calcium regulation, protein translation, and mitochondrial activity were the main cellular functions affected by Aβ oligomers (oAβ). We focused on SURF4, a protein that regulates the store-operated calcium channel (SOCE), and found that it contributes to oAβ(1-42) neurotoxicity by decreasing SOCE activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Ruth Nussinov, Hyunbum Jang, Attila Gursoy, Ozlem Keskin, Vadim Gaponenko
Summary: Drug action is related to blocking the mechanism of activation, not to whether the protein is in the active or inactive state.
CELL CHEMICAL BIOLOGY
(2021)