Article
Biochemistry & Molecular Biology
Dorota Kowalska, Joanna Dolzonek, Krzysztof Zamojc, Sergey A. Samsonov, Martyna Maszota-Zieleniak, Joanna Makowska, Piotr Stepnowski, Anna Bialk-Bielinska, Dariusz Wyrzykowski
Summary: Human serum albumin (HSA) plays a crucial role in binding low-molecular-weight compounds and facilitating their distribution in living organisms. This study investigates the impact of counter-ions, such as [B (CN)4]- and [C(CN)3]-, on the affinity of [IM1-12]+ towards HSA. Experimental methods and computational approaches are used to analyze protein-ligand interactions and the thermal stability of resulting complexes. The findings provide valuable insights into the presence of globular proteins and ionogenic compounds in the environment and living organisms.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Chemistry, Physical
Stanly Paul, Swathi Nadendla, M. Elizabeth Sobhia
Summary: The emergence of distinct variants has turned the COVID-19 pandemic into a global health challenge. Omicron, a new variant, has been classified as a variant of concern by the World Health Organization due to its higher mutation rate and accelerated human infection. Inhibition of the interaction between the receptor binding domain (RBD) and the human angiotensin converting enzyme-2 (ACE(2human)) receptor has been proven effective in inhibiting viral infection. Through molecular dynamics simulation, our study explores the atomic details and events of RBD-ACE(2human) interactions, providing insights for the development of therapeutic peptidomimetics targeting omicron.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2022)
Article
Biochemistry & Molecular Biology
Ieva Sutkeviciute, Ji Young Lee, Alex D. White, Christian Santa Maria, Karina A. Pena, Sofya Savransky, Pemra Doruker, Hongchun Li, Saifei Lei, Burak Kaynak, Chialing Tu, Lisa J. Clark, Subramaniam Sanker, Thomas J. Gardella, Wenhan Chang, Ivet Bahar, Jean-Pierre Vilardaga
Summary: By using molecular dynamics simulations and elastic network model-based methods, the study identified a key mechanical site that modulates the collective dynamics of PTHR and successfully identified selective small molecules with strong negative allosteric properties for PTHR signaling. This computational pipeline provides a way to detect precise druggable sites and identify allosteric modulators for GPCRs, expediting the discovery of small molecules as novel therapeutic candidates.
NATURE CHEMICAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Till El Harrar, Benedikt Frieg, Mehdi D. Davari, Karl-Erich Jaeger, Ulrich Schwaneberg, Holger Gohlke
Summary: This study investigates the impact of aqueous ionic liquids on a model enzyme through molecular dynamics simulations and finds that they can affect enzyme activity by modifying local structural stability, eventually leading to perturbations in the catalytic site and protein core. The identification of perturbation pathways and specific interactions with IL ions helps predict variant libraries with improved tolerance to aqueous ionic liquids.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Fufeng Liu, Wenjuan Wang, Zhenquan Xuan, Luying Jiang, Beibei Chen, Qinchen Dong, Fang Zhao, Wei Cui, Li Li, Fuping Lu
Summary: This study found that Fast Green FCF (FGF) can effectively inhibit Aβ-induced neurotoxicity by reducing Aβ fibrillogenesis, disintegrating mature fibrils, decreasing Aβ-induced cytotoxicity, and improving Aβ-induced learning and memory impairments. Molecular dynamics simulations demonstrated that FGF can interact with Aβ through various mechanisms to reduce its neurotoxic effects.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Biochemistry & Molecular Biology
Cheng Zhang, Nuria Codina, Jiazhi Tang, Haoran Yu, Nesrine Chakroun, Frank Kozielski, Paul A. Dalby
Summary: The research findings highlighted the different destabilizing pathways of protein structure under low pH and high temperature stress conditions, revealing the potential for stabilizing mutations in the CL domain and C-L-C(H)1 interface. The analysis also identified key salt bridge losses as a cause of conformational changes under different stresses, with implications for future engineering efforts to enhance stability.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Daniel P. Erickson, Martha Dunbar, Elham Hamed, Oguz K. Ozturk, Osvaldo H. Campanella, Sinan Keten, Bruce R. Hamaker
Summary: The study revealed that specific peptide segments in corn protein variants tend to maintain stable aggregates and beta-sheet structures. Simulations showed that stability is influenced by the initial orientation and the presence of contiguous small hydrophobic residues. Peptide sequences without proline may have higher levels of beta-sheet structuring.
Article
Chemistry, Physical
Nisha Amarnath Jonniya, Md Fulbabu Sk, Parimal Kar
Summary: The WNK kinase is important in blood pressure regulation, with WNK1 being a potential target for hypertension treatment. Allosteric inhibitors, binding to non-conserved sites, induce structural changes that render the kinase inactive. Understanding these mechanisms may aid in the design of specific inhibitors against WNK1.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2021)
Review
Biochemistry & Molecular Biology
Alessandro Berselli, Fabio Benfenati, Luca Maragliano, Giulio Alberini
Summary: Claudins (Cldns) are transmembrane proteins that play a major role in tight junction integrity and tissue selectivity. Computational methodologies have been used to investigate the properties of Cldn and provide valuable insights for improving the characterization of Cldn and designing strategies for controlling paracellular transport.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Alessandro Berselli, Fabio Benfenati, Luca Maragliano, Giulio Alberini
Summary: Claudins are transmembrane proteins that play a crucial role in tight junction integrity and tissue selectivity. They form barriers or ion-selective channels between cells in the paracellular space. Computational methodologies have helped to elucidate the properties of Claudins and could be useful for designing strategies to control the transport of drugs or molecules.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Akshatha Hebbar, Poulumi Dey, Anoop Kishore Vatti
Summary: This study investigated the impact of six different mixed solvents on the structure of lysozyme using molecular dynamics simulations. The results showed that most mixed solvents led to a more compact and rigid lysozyme structure, while two solvents caused structural expansion. The interactions between lysozyme and solvents as well as the increase in surface area were also analyzed, providing insights into the overall stability of lysozyme.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
J. R. Fleming, D. J. Rigden, O. Mayans
Summary: This article discusses the importance of therapeutic significance and classification methods of nsSNVs in titin. It focuses on the T2580I mutation and proposes that considering the higher order structure of the titin chain is necessary for accurate prediction and assessment of nsSNVs.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Multidisciplinary Sciences
N. Gao, Z. W. Yao, G. H. Lu, H. Q. Deng, F. Gao
Summary: The study found a new diffusion mechanism for <100> interstitial dislocation loops in BCC iron using self-adaptive accelerated molecular dynamics, which represents a significant step towards understanding the mechanical behavior and microstructure evolution of the material.
NATURE COMMUNICATIONS
(2021)
Review
Agriculture, Multidisciplinary
Abraham Vidal-Limon, Jose E. Aguilar-Toala, Andrea M. Liceaga
Summary: The use of in silico tools, such as molecular docking, to study biological activity of proteins and peptides can sometimes produce results that do not correlate with actual experimental binding affinities. Molecular dynamics simulations (MDS) offer a solution to overcome sampling limitations in docking analysis and provide valuable information in deciphering functional mechanisms of proteins and peptides. This review discusses the traditional use of in silico models, like molecular docking, and highlights the importance of MDS in predicting structural and functional dynamics of food proteins and bioactive peptides.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Tibo Duran, Bruna Minatovicz, Ryan Bellucci, Jun Bai, Bodhisattwa Chaudhuri
Summary: This study investigates the effect of freezing rates on the stability of protein lysozyme using molecular dynamics simulations. The results show that faster freezing rates better maintain protein stability, resulting in less secondary structure deviations, higher hydration level, and structural compactness. The study also identifies the residues near and within specific helices that contribute to the structural instability of lysozyme at the freezing temperature of 247 K.
PHARMACEUTICAL RESEARCH
(2022)
Article
Chemistry, Multidisciplinary
Xiaoqin Pan, Xuan Lin, Dongsheng Cao, Xiangxiang Zeng, Philip S. Yu, Lifang He, Ruth Nussinov, Feixiong Cheng
Summary: This review introduces guidelines on utilizing deep learning methodologies and tools for drug repurposing, which is of great importance in drug development. The article summarizes the commonly used bioinformatics and pharmacogenomics databases for drug repurposing and discusses the recently developed sequence-based and graph-based representation approaches as well as state-of-the-art deep learning-based methods. The applications of drug repurposing in fighting the COVID-19 pandemic are presented, along with an outline of future challenges.
WILEY INTERDISCIPLINARY REVIEWS-COMPUTATIONAL MOLECULAR SCIENCE
(2022)
Review
Multidisciplinary Sciences
Ruth Nussinov, Chung-Jung Tsai, Hyunbum Jang
Summary: The question of how the same gene mutations can lead to both cancer and neurodevelopmental disorders has always been puzzling. This article reviews the literature and proposes that factors such as cell type-specific expression of the mutant protein, timing of activation, and the absolute number of molecules involved play key roles in determining the pathological phenotypes.
Review
Biochemistry & Molecular Biology
Ruth Nussinov, Chung-Jung Tsai, Hyunbum Jang
Summary: This article discusses the concept of productive signaling, including its definition, measurement, and determining factors. It highlights the importance of understanding signal propagation in diseases like cancer and neurodevelopmental disorders. The authors propose a framework for investigating signal transduction by defining cellular processes, conducting experimental measurements, and utilizing computational AI algorithms.
BIOPHYSICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Yonglan Liu, Mingzhen Zhang, Hyunbum Jang, Ruth Nussinov
Summary: Bcr-Abl, a nonreceptor tyrosine kinase, plays a crucial role in leukemias, particularly chronic myeloid leukemia (CML). The fusion of Bcr and Abl leads to constitutive activation of Bcr-Abl. Oligomerization of Bcr-Abl is critical for its membrane clustering, MAPK signaling, and cell proliferation. Understanding the structural basis of Bcr-Abl oligomerization can guide the development of novel drugs targeting this process.
Article
Cell Biology
Chunyang Yi, Jiacheng He, Dan Huang, Yumiao Zhao, Chan Zhang, Xiyun Ye, Ying Huang, Ruth Nussinov, Junke Zheng, Mingyao Liu, Weiqiang Lu
Summary: Activation of the orphan GPCR GPR132 induces cell differentiation in acute myeloid leukemia (AML) and the natural product 8-gingerol is found to be a potential GPR132 agonist, promoting differentiation and reducing colony formation in AML cell lines.
CELL DEATH & DISEASE
(2022)
Letter
Oncology
Mingzhen Zhang, Ryan Maloney, Yonglan Liu, Hyunbum Jang, Ruth Nussinov
CANCER COMMUNICATIONS
(2023)
Review
Cell Biology
Xiangxiang Zeng, Fei Wang, Yuan Luo, Seung-Gu Kang, Jian Tang, Felice C. Lightstone, Evandro F. Fang, Wendy Cornell, Ruth Nussinov, Feixiong Cheng
Summary: The recent advances of AI and deep generative models in medicinal applications, specifically in drug discovery and development, have proven their utility. This review provides an updated and accessible guide for the computational drug discovery and development community, discussing classical and newly developed AI approaches. The theoretical frameworks for representing chemical and biological structures and their applications are described, along with the challenges and future directions of multimodal deep generative models for accelerating drug discovery.
CELL REPORTS MEDICINE
(2022)
Article
Chemistry, Multidisciplinary
Alix Troester, Michael DiPrima, Nathalie Jores, Denis Kudlinzki, Sridhar Sreeramulu, Santosh L. Gande, Verena Linhard, Damian Ludig, Alexander Schug, Krishna Saxena, Maria Reinecke, Stephanie Heinzlmeir, Matthias S. Leisegang, Jan Wollenhaupt, Frank Lennartz, Manfred S. Weiss, Bernhard Kuster, Giovanna Tosato, Harald Schwalbe
Summary: In this study, a series of derivatives of the EPHA2 inhibitor NVP-BHG712 and triazine-based compounds were synthesized and evaluated. Eight inhibitors showed high affinity for EPHA2. Testing in seven colon cancer cell lines revealed promising effects of some derivatives for the control of human colon carcinoma.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Review
Pharmacology & Pharmacy
Ruth Nussinov, Mingzhen Zhang, Yonglan Liu, Hyunbum Jang
Summary: Drug discovery is a highly challenging and significant interdisciplinary aim. The success of AlphaFold, an AI-powered technology, has raised hopes for drug discovery, but its limitations need to be considered. Improving AlphaFold's performance in active state models can enhance the success rate of rational drug design.
DRUG DISCOVERY TODAY
(2023)
Article
Chemistry, Physical
Mingzhen Zhang, Yonglan Liu, Hyunbum Jang, Ruth Nussinov
Summary: Kinase drug selectivity is a challenge in cancer research. Researchers propose a protocol to identify unique geometric features in the drug pocket that can distinguish one kinase from others. They analyze the structural principles of kinase drug selectivity using experimental structures and artificial intelligence. The results show that there are binary units in the kinome that can distinguish kinases from each other.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2023)
Review
Biophysics
Ruth Nussinov, Bengi Ruken Yavuz, M. Kaan Arici, Habibe Cansu Demirel, Mingzhen Zhang, Yonglan Liu, Chung-Jung Tsai, Hyunbum Jang, Nurcan Tuncbag
Summary: Neurodevelopmental disorders (NDDs) and cancer have similarities in terms of proteins, pathways, and mutations, but have different clinical symptoms. However, individuals with NDDs have a higher likelihood of developing cancer later on. This review explores how shared features can result in different medical conditions and why having an NDD first can increase the chances of malignancy.
BIOPHYSICAL REVIEWS
(2023)
Article
Chemistry, Medicinal
Alix Troster, Nathalie Jores, Konstantin S. Mineev, Sridhar Sreeramulu, Michael DiPrima, Giovanna Tosato, Harald Schwalbe
Summary: This concept paper describes the general strategies for EPHA2 inhibition with small molecules and summarizes the potential of targeting EPHA2 in CRC. EPHA2 plays a crucial role in the development and resistance mechanisms of CRC.
Article
Genetics & Heredity
Bengi Ruken Yavuz, M. Kaan Arici, Habibe Cansu Demirel, Chung-Jung Tsai, Hyunbum Jang, Ruth Nussinov, Nurcan Tuncbag
Summary: Epidemiological studies show that individuals with neurodevelopmental disorders are more likely to develop certain types of cancer. While these disorders and cancer share proteins, pathways, and mutations, they differ in clinical outcomes. The key factor determining clinical outcome is signaling strength, with strong signaling promoting cell proliferation in cancer and moderate signaling affecting differentiation in neurodevelopmental disorders.
NPJ GENOMIC MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Ruth Nussinov, Yonglan Liu, Wengang Zhang, Hyunbum Jang
Summary: The propensities of protein conformations can predict cell function and suggest drug efficiency.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Ruth Nussinov, Yonglan Liu, Wengang Zhang, Hyunbum Jang
Summary: The sequence-structure-function paradigm in molecular biology has been updated to include the concept of conformational ensembles, recognizing that proteins are dynamic and constantly transitioning between different conformational states. The number and stability of these states are crucial for protein function. Understanding conformational propensities is essential for studying diverse systems and can provide insights into the dynamics of protein ensembles in cells.
RSC CHEMICAL BIOLOGY
(2023)
