Article
Chemistry, Physical
Saied Habibian Dehkordi, Sadegh Farhadian, Mohammad Ghasemi
Summary: The experimental results demonstrated that Tar can bind to α-Chy and effectively quench its intrinsic fluorescence through the static quenching mechanism. Thermodynamic data showed that van der Waals interactions and hydrogen bonds played a leading role in stabilizing the α-Chy-Tar complex. Circular dichroism results revealed a change in the secondary structural components of α-Chy during the binding of Tar.
JOURNAL OF MOLECULAR LIQUIDS
(2021)
Article
Chemistry, Multidisciplinary
Pritam Biswas, Uttam Pal, Aniruddha Adhikari, Susmita Mondal, Ria Ghosh, Dipanjan Mukherjee, Tanusri Saha-Dasgupta, Sudeshna Shyam Choudhury, Ranjan Das, Samir Kumar Pal
Summary: This study investigates the conformational dynamics and catalytic activity of alpha-chymotrypsin using optical spectroscopy and molecular dynamics simulations. The enzyme shows highest catalytic efficiency at the optimum temperature of 308 K. It is found that the flexibility of the enzyme increases with temperature. Principal component analysis reveals the essential dynamics and gatekeeping role of loop regions surrounding the catalytic pocket.
Article
Chemistry, Analytical
Helisa H. Wippel, Juan D. Chavez, Andrew D. Keller, James E. Bruce
Summary: The XL-MS technique provides insight into protein conformations and interactions within their cellular environment, while the iqPIR strategy allows for comparative interactome studies using isotope encoded chemical cross-linkers. Multiplexed iqPIR enables quantitative interactome analysis of up to six biological samples in a single LC-MS acquisition, revealing specific protein conformational and interaction changes in response to different inhibitors.
ANALYTICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Yang Huang, Zizhen Li, Qiyang Hong, Lizhi Zhou, Yue Ma, Yisha Hu, Jiabao Xin, Tingting Li, Zhibo Kong, Qingbing Zheng, Yixin Chen, Qinjian Zhao, Ying Gu, Jun Zhang, Yingbin Wang, Hai Yu, Shaowei Li, Ningshao Xia
Summary: Conformational changes during biomolecular recognition are crucial for understanding allosteric mechanisms. In this study, the researchers used molecular dynamics simulations to investigate the conformational changes of the 13D4 antibody during recognition. They developed a stepwise docking MD method that accurately reproduced the conformational changes observed in the co-crystal structure.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Article
Spectroscopy
Shuqi Guo, Qiang Zhao, Yuze Li, Shanshan Chu, Falin He, Xiangxiang Li, Ning Sun, Wansong Zong, Rutao Liu
Summary: This study investigated the mechanism of how Bisphenol A (BPA) affects the activity of alpha-chymotrypsin, a proteolytic enzyme. The results showed that BPA caused changes in the structure of alpha-chymotrypsin, leading to an increase in its activity. This study filled the research gap on the mechanism of BPA on proteolytic enzymes and provided a reliable basis for disease prevention.
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
(2023)
Article
Multidisciplinary Sciences
Matthias M. Schneider, Saurabh Gautam, Therese W. Herling, Ewa Andrzejewska, Georg Krainer, Alyssa M. Miller, Victoria A. Trinkaus, Quentin A. E. Peter, Francesco Simone Ruggeri, Michele Vendruscolo, Andreas Bracher, Christopher M. Dobson, F. Ulrich Hartl, Tuomas P. J. Knowles
Summary: Molecular chaperones play a role in maintaining cellular protein homeostasis by assisting in protein folding and preventing amyloid formation. Chaperones from the Hsp70 family can disaggregate protein aggregates, including amyloids, with the Hsc70-DnaJB1-Apg2 system directly removing single molecules from fibril ends.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Zahra Musavizadeh, Alessandro Grottesi, Giulia Guarguaglini, Alessandro Paiardini
Summary: The study reveals the impact of phosphorylation on the stability of the A-loop and the effect of conformation disrupting inhibitors on the dynamics of Aurora-A. The presence of a phosphate moiety induces Aurora-A to sample two distinct energy minima, indicating a significant difference in conformational distributions compared to the unphosphorylated state.
Article
Chemistry, Multidisciplinary
Congcong Li, Siao Chen, Tianci Huang, Fangning Zhang, Jiawei Yuan, Hao Chang, Wannan Li, Weiwei Han
Summary: Molecular dynamics simulations revealed the impact of substrate analogues DON and cPRPP on the structural stability of GPATase, with cPRPP affecting the formation of the R73-DON salt bridge by binding to the PRTase flexible loop. This study also found that binding of DON and cPRPP to the two domains of GPATase facilitated the movement of the glutamine loop and the PRTase flexible loop closer together, promoting the transfer of NH3 via the NH3 channel.
FRONTIERS IN CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Matthew S. Bluma, Kathryn M. Schultz, Christopher J. Kristich, Candice S. Klug
Summary: Many bacterial genomes contain a transmembrane protein kinase called PASTA kinase, which plays a crucial role in controlling various processes in bacterial pathogens. The crystal structures of PASTA kinase domains reveal a familiar structure with a centrally located activation loop that becomes phosphorylated and regulates downstream signaling pathways. Previous studies have identified several phosphorylation sites on the activation loop of a PASTA kinase, but the mechanism by which loop phosphorylation regulates its function remains unknown.
Article
Biochemistry & Molecular Biology
Sepehr Dehghani-Ghahnaviyeh, Karan Kapoor, Emad Tajkhorshid
Summary: This study used molecular dynamics simulations to investigate the ATP hydrolysis-induced conformational changes in Pgp nucleotide-binding domains (NBDs), revealing that ATP/ADP exchange induced conformational changes within the conserved signature motif of NBDs, resulting in relative orientational changes. Furthermore, putative hydrolysis-competent configurations were captured, with a conserved glutamate in the Walker-B motif acting as a catalytic base capturing a water molecule likely initiating ATP hydrolysis.
Article
Biochemistry & Molecular Biology
Ye Liu, Yan Li, Sijin Wu, Guohui Li, Huiying Chu
Summary: In this study, we revealed the dynamic cooperative molecular mechanism of PGK1 conformational transition with products releasing, as well as the influence of post translational modifications (PTMs).
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Bhawna Dixit, Wim Vranken, An Ghysels
Summary: In this study, the impact of mutations and glycosylation on the conformational dynamics of alpha-1 acid glycoprotein (AGP) was investigated using molecular dynamics simulations and sequence-based dynamics predictions. The researchers found that glycosylation decreased the local backbone flexibility of AGP while increasing the flexibility of distant regions through allosteric effects. Mutations near the glycosylation site were observed to affect the conformational preferences of the glycans. These findings provide insights into the control of glycan dynamics by mutations and its direct influence on protein backbone flexibility, which could be useful in drug design targeting AGP's glycosylation and cancer mutations.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2023)
Article
Multidisciplinary Sciences
Amy Rice, Sourav Haldar, Eric Wang, Paul S. Blank, Sergey A. Akimov, Timur R. Galimzyanov, Richard W. Pastor, Joshua Zimmerberg
Summary: This study reveals that the synthesized fusion peptides of influenza virus can actively form pores in membranes, explaining the hemolytic activity of the virus and the formation of liposome pores observed in cryo-electron tomography. Molecular dynamics simulations show that the fusion peptides aggregate heterogeneously in the membrane, leading to changes in membrane structure and the formation of hybrid bilayer nanodomains. This research is crucial for understanding membrane poration during viral fusion.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Samuel G. Holmes, Balaji Nagarajan, Umesh R. Desai
Summary: This study discovered novel compact topologies of heparan sulfate (HS) that are influenced by the 3-O-sulfation of cis-idoA residues. The transition in HS topology is driven by rotations that reduce like-charge repulsion, release water molecules, and establish specific interactions. These findings reveal a dynamic sulfation code in natural HS that could be utilized for selective recognition of target proteins.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Article
Biology
Brandon Havranek, Graeme Walker Lindsey, Yusuke Higuchi, Yumi Itoh, Tatsuya Suzuki, Toru Okamoto, Atsushi Hoshino, Erik Procko, Shahidul M. M. Islam
Summary: SARS-CoV-2, especially the B.1.1.529/omicron variant, is mutating to evade antibodies from vaccination and monoclonal antibodies. A computational design strategy was used to develop an affinity-enhanced ACE2 decoy, FLIF, which showed tight binding to SARS-CoV-2 delta and omicron variants. FLIF demonstrated therapeutic efficacy against a broad range of SARS-CoV-2 variants and neutralized omicron BA.5 in vitro and in vivo.
COMMUNICATIONS BIOLOGY
(2023)
Article
Chemistry, Physical
Nasrollah Rezaei-Ghaleh, Giacomo Parigi, Markus Zweckstetter
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2019)
Article
Multidisciplinary Sciences
Salvatore Mamone, Nasrollah Rezaei-Ghaleh, Felipe Opazo, Christian Griesinger, Stefan Gloeggler
Article
Chemistry, Multidisciplinary
Farhang Aliakbari, Hossein Mohammad-Beigi, Shahsanam Abbasi, Nasrollah Rezaei-Ghaleh, Frederik Lermyte, Soha Parsafar, Stefan Becker, Azita Parvaneh Tafreshi, Peter B. O'Connor, Joanna F. Collingwood, Gunna Christiansen, Duncan S. Sutherland, Poul Henning Jensen, Dina Morshedi, Daniel E. Otzen
Summary: Incorporation of baicalein into zwitterionic nanoliposomes successfully addresses the stability and solubility issues, making NLP-Ba effective in inhibiting alpha-synuclein fibrillation associated with Parkinson's disease. This nanosystem shows potential neuroprotective effects and could be a promising therapeutic option against PD.
ADVANCED FUNCTIONAL MATERIALS
(2021)
Article
Biochemistry & Molecular Biology
Juan Carlos Fuentes-Monteverde, Stefan Becker, Nasrollah Rezaei-Ghaleh
Summary: In this study, Na-23 NMR was used to investigate the internal fluidity of biomolecular condensed phases, demonstrating its potential in agarose gels and peptide hydrogels. The research also revealed the presence of multiple microscopic environments within the water-triethylamine mixture.
Article
Chemistry, Physical
Salvatore Mamone, Stefan Gloeggler, Stefan Becker, Nasrollah Rezaei-Ghaleh
Summary: The amyloid cascade hypothesis suggests that Aβ aggregation is the initial trigger of Alzheimer's disease, with Aβ42 having higher aggregation propensity than Aβ40. The C-terminal region of Aβ, especially the G33-L34-M35 segment, plays a specific role in the early stages of Aβ aggregation, providing a target for the rational design of Aβ42 aggregation inhibitors.
Article
Biochemistry & Molecular Biology
Hadi Nedaei, Nasrollah Rezaei-Ghaleh, Karin Giller, Stefan Becker, Leila Karami, Ali Akbar Moosavi-Movahedi, Christian Griesinger, Ali Akbar Saboury
Summary: Alzheimer's disease is characterized by the presence of extraneuronal amyloid plaques composed of amyloid-beta (A beta) fibrillar aggregates in the brains of patients. Previous research has shown that atorvastatin, a cholesterol-lowering drug, can decrease the production of cerebral A beta in mouse models. This study explores the direct effect of atorvastatin on A beta 42 aggregation and finds that it promotes aggregation, likely due to the presence of calcium ions. However, this effect can be reversed by removing calcium ions.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Chemistry, Physical
Sahithya Phani Babu Vemulapalli, Stefan Becker, Christian Griesinger, Nasrollah Rezaei-Ghaleh
Summary: The presence of salt bridges between Arg5 and its nearby negatively charged residues in the N-terminal region of Aβ is correlated with less extended structures. Ser8 phosphorylation promotes Aβ aggregation, and density functional theory calculations demonstrate how negatively charged phosphoserine 8 influences the network of adjacent salt bridges.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2021)
Article
Chemistry, Multidisciplinary
Nasrollah Rezaei-Ghaleh, Jaime Agudo-Canalejo, Christian Griesinger, Ramin Golestanian
Summary: The researchers investigated the molecular diffusivity of reactants, catalyst, and product in a copper-catalyzed click reaction. They developed new NMR diffusion methods and found that while the reactants showed decreased diffusivity over time, the product showed increased diffusivity and the catalyst showed slight diffusion enhancement. This suggests the presence of a relatively large intermediate species with lower diffusivity than the reactants and product.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Physical
Christian F. Pantoja, Markus Zweckstetter, Nasrollah Rezaei-Ghaleh
Summary: Biomolecular phase separation is crucial for the spatial organization of cellular activities. The dynamic formation and rapid component exchange between phase separated cellular bodies and their environment are essential for their function. The NMR-based approach developed in this study allows quantitative monitoring of the effect of regulatory factors on component exchange and facilitates exchange-based screening and optimization of small molecules against druggable biomolecular targets located inside condensed phases.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2022)
Article
Chemistry, Multidisciplinary
Nasrollah Rezaei-Ghaleh
Summary: In this study, we investigated the dynamic behavior of water molecules in saturated alkali chloride solutions. Our results show that water molecules maintain a high level of mobility in these solutions, independent of adjacent ions.
Editorial Material
Chemistry, Multidisciplinary
Nasrollah Rezaei-Ghaleh, Jaime Agudo-Canalejo, Christian Griesinger, Ramin Golestanian
Summary: This article responds to the comments from Huang and Granick regarding the diffusion NMR measurements of molecules during copper-catalyzed click reaction, providing further arguments and new data to support the conclusion that there is no boosted mobility observed for the reactants and product during the reaction.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Biochemistry & Molecular Biology
Daniel Sieme, Christian Griesinger, Nasrollah Rezaei-Ghaleh
Summary: Heparins and heparan sulfate polysaccharides play important roles in cell-to-matrix and cell-to-cell signaling processes. In this study, a Na-23 NMR-based competition assay was developed to monitor metal ion binding to heparin and the release of sodium ions. The results showed that there are at least two metal ion-binding sites on heparin, potentially undergoing dynamic exchange.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Anton Abyzov, Eckhard Mandelkow, Markus Zweckstetter, Nasrollah Rezaei-Ghaleh
Summary: The dynamics of a 441-residue long intrinsically disordered protein (IDP), tau protein, were investigated in the temperature range of 0-25 degrees C. The results suggest that at higher temperatures, the fast backbone conformational fluctuations and slower chain segmental motions of the protein might become inseparable. This study demonstrates the remarkable dynamic plasticity of this prototypical IDP and highlights the need for dynamic studies of IDPs at multiple temperatures.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Physical
Nasrollah Rezaei-Ghaleh, Mehriar Amininasab, Karin Giller, Stefan Becker
Summary: Amyloid-beta (Afi) deposition is a pathological hallmark of Alzheimer's disease (AD). This study investigates the influence of AD-related mutations on the stability of Afi aggregates using NMR spectroscopy and MD simulation. The results show that different mutations alter the pressure stability of Afi40 aggregates in distinct manners. Our data propose a structural basis for the distinct stability of various Afi fibrils and highlight stability as a potential molecular property contributing to the heterogeneity of amyloid pathology in AD.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2023)
Article
Chemistry, Multidisciplinary
Nasrollah Rezaei-Ghaleh, Francesca Munari, Stefan Becker, Michael Assfalg, Christian Griesinger
CHEMICAL COMMUNICATIONS
(2019)