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Biochemistry & Molecular Biology
Xiao-Xuan Shi, Peng-Ye Wang, Hong Chen, Ping Xie
Summary: Through all-atom molecular dynamics simulations, it was found that the kinesin head's strong and weak interactions with the microtubule can induce rapid large conformational changes in the tubulin, significantly affecting their binding energy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Medicinal
Christoph Oehlknecht, Sonja Katz, Christina Kroess, Bernhard Sprenger, Petra Engele, Rainer Schneider, Chris Oostenbrink
Summary: The article introduces an efficient method for calculating protein binding free energies by combining the one-step perturbation and the third-power fitting approach. Experimental in silico saturation mutagenesis confirms the method's high accuracy in predicting relative free energies of amino acid mutations.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Biochemistry & Molecular Biology
Siyuan Song, Qinghong Shi
Summary: The outbreak of COVID-19 has led to an urgent need for advanced diagnosis and vaccination globally. The discovery of high-affinity ligands is crucial for the production of vaccines and diagnostic reagents. This study introduced a virtual library for screening ZRBD affibody ligands that target the receptor binding domain of the spike protein. Through molecular docking and dynamics simulations, three potential ZRBD affibodies were identified and their high affinity for RBD binding was confirmed.
Article
Biology
Remy A. Yovanno, Tsung Han Chou, Sarah J. Brantley, Hiro Furukawa, Albert Y. Lau
Summary: This study investigated the mechanisms of D-serine in receptor activation and found that D-serine competes with glutamate for binding to GluN2A. The inhibitory effect of D-serine at high concentrations was confirmed through electrophysiology experiments.
Article
Biochemistry & Molecular Biology
Vivek Modi, Roland L. Dunbrack
Summary: The study clustered kinase structures and provided an accessible resource Kincore, allowing users to query the database for conformational states and inhibitor types. This will aid in understanding the conformational dynamics of proteins and guide the development of inhibitors targeting specific states.
NUCLEIC ACIDS RESEARCH
(2022)
Review
Cell Biology
Ghada S. Hassan, Suzanne Salti, Walid Mourad
Summary: CD154, an inflammatory mediator, interacts with integrins and affects various biological processes such as thrombus formation, cell activation, and release of pro-inflammatory mediators. This article summarizes the interactions between different integrins and CD154 and their importance in pro-inflammatory and apoptotic responses.
Article
Biochemistry & Molecular Biology
Qian Jia, Hui Zeng, Mingwei Li, Jing Tang, Nan Xiao, Shangfang Gao, Huanxi Li, Jinbing Zhang, Zhiyong Zhang, Wei Xie
Summary: This study investigates the structure and function of guanosine deaminase (GSDA). By analyzing the cocrystal structures of Arabidopsis thaliana GSDA bound by inactive guanosine derivatives, it is found that the binding performances of the two protomers are unequal, and molecular dynamics simulation confirms diverse conformations during the enzyme-ligand interactions. Furthermore, tripartite salt bridges between subunits are identified to play a role as gating systems for substrate binding and product release.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Kwabena Owusu Dankwah, Jonathon E. Mohl, Khodeza Begum, Ming-Ying Leung
Summary: This study computationally predicted the binding of a single ligand to GPCRs from different families and uncovered similar binding pockets that contribute to ligand interactions. These findings can be applied to improve protein function inference, drug repurposing, drug toxicity prediction, and the acceleration of new drug development.
Article
Chemistry, Physical
Katsuhiro Endo, Daisuke Yuhara, Kenji Yasuoka
Summary: In this study, a new sampling method called continuous normalizing molecular flow (CNMF) is proposed for Monte Carlo molecular simulation. The CNMF method generates samples by solving a first-order differential equation with two-body intermolecular interaction terms. It is demonstrated that Monte Carlo molecular simulation using CNMF is more efficient than the standard simulation.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2022)
Article
Biochemistry & Molecular Biology
Elizabeth K. M. Johnstone, Heng B. See, Rekhati S. Abhayawardana, Angela Song, K. Johan Rosengren, Stephen J. Hill, Kevin D. G. Pfleger
Summary: Receptor heteromerization involves complex formation between at least two different receptors with distinct pharmacology, necessitating the use of Receptor-HIT technology for detection and analysis of pharmacological functions. This study for the first time utilized BRET and fluorescently-labeled ligands to investigate receptor heteromerization on the cell surface effectively.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Physical
Shima Arasteh, Bin W. Zhang, Ronald M. Levy
Summary: The R-FEP-R 2.0 method is used to estimate conformational free energy changes of protein loops via an alchemical path. Unlike other sampling algorithms, R-FEP-R and R-FEP-R 2.0 do not require predetermined collective coordinates and transition pathways.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2021)
Article
Biochemistry & Molecular Biology
Jake Zheng Chen, William Bret Church, Karine Bastard, Anthony P. Duff, Thomas Balle
Summary: This article investigates the molecular mechanisms of a mutation (Ser688Tyr) in the NMDAR GluN1 ligand binding domain that causes encephalopathies. The mutation leads to instability of ligands and changes in receptor activity.
Article
Biochemistry & Molecular Biology
Marton Gadanecz, Zsolt Fazekas, Gyula Palfy, Dora Karancsine Menyhard, Andras Perczel
Summary: In this study, the catalytically significant states of the oncogenic G12C variant of KRAS were determined using CS-Rosetta software and NMR-data-driven molecular dynamics simulations. The flexibility of the Switch-I and Switch-II regions limited the collection of chemical shift information for the most important regions. A torsional restraint set was developed based on the CS-Rosetta ensembles to override the force-field-based parametrization and allow for complete models with structural features and heterogeneity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Physical
Samuel C. Gill, David L. Mobley
Summary: This study successfully samples multiple binding modes of a ligand in a single molecular dynamics simulation by developing a novel Monte Carlo move called MolDarting and coupling it with NCMC. The method shows significantly increased acceptance rates in testing phases compared to uniformly sampling internal and rotational/translational degrees of freedom in these systems.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2021)
Article
Biochemistry & Molecular Biology
Atsushi Furukawa, Yusuke Shuchi, Jiaqi Wang, Pablo Adrian Guillen-Poza, Shigenari Ishizuka, Misuzu Kagoshima, Risa Ikeno, Hiroyuki Kumeta, Sho Yamasaki, Takanori Matsumaru, Takashi Saitoh, Katsumi Maenaka
Summary: In this study, the mechanism of Mincle receptor recognizing trehalose dimycolate (TDM) was investigated using nuclear magnetic resonance analysis. The results showed that Mincle may have different binding modes for different types of glycolipids, which is important for rational adjuvant development.