Probing the role of the protonation state of a minor groove-linker histidine in Exd-Hox-DNA binding
Biophys J. 2023 Dec 20:S0006-3495(23)04151-6. doi: 10.1016/j.bpj.2023.12.013. Online ahead of print.ABSTRACTDNA recognition and targeting by transcription factors (TFs) through specific binding are fundamental in biological processes. Furthermore, the histidine protonation state at the TF-DNA binding interface can significantly influence the binding mechanism of TF-DNA complexes. Nevertheless, the role of histidine in TF-DNA complexes remains underexplored. Here, we employed all-atom molecular dynamics simulations using AlphaFold2-modeled complexes based on previously solved co-crystal structures to probe the role of the H...
Source: Biophysical Journal - December 22, 2023 Category: Physics Authors: Yibei Jiang Tsu-Pei Chiu Raktim Mitra Remo Rohs Source Type: research
Insights into Nucleic Acid Helix Formation from Infrared Spectroscopy
Biophys J. 2023 Dec 20:S0006-3495(23)04155-3. doi: 10.1016/j.bpj.2023.12.017. Online ahead of print.NO ABSTRACTPMID:38130057 | DOI:10.1016/j.bpj.2023.12.017 (Source: Biophysical Journal)
Source: Biophysical Journal - December 22, 2023 Category: Physics Authors: Susan J Schroeder Source Type: research
Resurgent current in context: Insights from the structure and function of Na and K channels
Biophys J. 2023 Dec 20:S0006-3495(23)04154-1. doi: 10.1016/j.bpj.2023.12.016. Online ahead of print.ABSTRACTDiscovered just over twenty-five years ago in cerebellar Purkinje neurons, resurgent Na current was originally described operationally as a component of voltage-gated Na current that flows upon repolarization from relatively depolarized potentials and speeds recovery from inactivation, increasing excitability. Its presence in many excitable cells and absence from others has raised questions of its biophysical and molecular mechanisms. Early studies proposed that Na channels capable of generating resurgent current are...
Source: Biophysical Journal - December 22, 2023 Category: Physics Authors: Teresa K Aman Indira M Raman Source Type: research
Probing the role of the protonation state of a minor groove-linker histidine in Exd-Hox-DNA binding
Biophys J. 2023 Dec 20:S0006-3495(23)04151-6. doi: 10.1016/j.bpj.2023.12.013. Online ahead of print.ABSTRACTDNA recognition and targeting by transcription factors (TFs) through specific binding are fundamental in biological processes. Furthermore, the histidine protonation state at the TF-DNA binding interface can significantly influence the binding mechanism of TF-DNA complexes. Nevertheless, the role of histidine in TF-DNA complexes remains underexplored. Here, we employed all-atom molecular dynamics simulations using AlphaFold2-modeled complexes based on previously solved co-crystal structures to probe the role of the H...
Source: Biophysical Journal - December 22, 2023 Category: Physics Authors: Yibei Jiang Tsu-Pei Chiu Raktim Mitra Remo Rohs Source Type: research
Insights into Nucleic Acid Helix Formation from Infrared Spectroscopy
Biophys J. 2023 Dec 20:S0006-3495(23)04155-3. doi: 10.1016/j.bpj.2023.12.017. Online ahead of print.NO ABSTRACTPMID:38130057 | DOI:10.1016/j.bpj.2023.12.017 (Source: Biophysical Journal)
Source: Biophysical Journal - December 22, 2023 Category: Physics Authors: Susan J Schroeder Source Type: research
Resurgent current in context: Insights from the structure and function of Na and K channels
Biophys J. 2023 Dec 20:S0006-3495(23)04154-1. doi: 10.1016/j.bpj.2023.12.016. Online ahead of print.ABSTRACTDiscovered just over twenty-five years ago in cerebellar Purkinje neurons, resurgent Na current was originally described operationally as a component of voltage-gated Na current that flows upon repolarization from relatively depolarized potentials and speeds recovery from inactivation, increasing excitability. Its presence in many excitable cells and absence from others has raised questions of its biophysical and molecular mechanisms. Early studies proposed that Na channels capable of generating resurgent current are...
Source: Biophysical Journal - December 22, 2023 Category: Physics Authors: Teresa K Aman Indira M Raman Source Type: research
Direct inhibition of human APOBEC3 deaminases by HIV-1 Vif independent of the proteolysis pathway
In this study, we elucidate that VβBCC inhibits deamination by A3G, A3F, and A3B, independently of proteasomal degradation. Surprisingly, we discovered that this inhibition for A3G is directly attributed to the interaction between VβBCC and the C-terminal domain of A3G. Previously, it was believed that Vif did not interact with the C-terminal domain. Our findings suggest that inhibiting the interaction between VβBCC and the C-terminal domain, as well as the N-terminal domain known to be targeted for ubiquitination, of A3G may be needed to prevent counteraction by Vif. Significance An accessory protein of HIV-1, Vif, cou...
Source: Biophysical Journal - December 20, 2023 Category: Physics Authors: Keisuke Kamba Li Wan Satoru Unzai Ryo Morishita Akifumi Takaori-Kondo Takashi Nagata Masato Katahira Source Type: research
Direct inhibition of human APOBEC3 deaminases by HIV-1 Vif independent of the proteolysis pathway
In this study, we elucidate that VβBCC inhibits deamination by A3G, A3F, and A3B, independently of proteasomal degradation. Surprisingly, we discovered that this inhibition for A3G is directly attributed to the interaction between VβBCC and the C-terminal domain of A3G. Previously, it was believed that Vif did not interact with the C-terminal domain. Our findings suggest that inhibiting the interaction between VβBCC and the C-terminal domain, as well as the N-terminal domain known to be targeted for ubiquitination, of A3G may be needed to prevent counteraction by Vif. Significance An accessory protein of HIV-1, Vif, cou...
Source: Biophysical Journal - December 20, 2023 Category: Physics Authors: Keisuke Kamba Li Wan Satoru Unzai Ryo Morishita Akifumi Takaori-Kondo Takashi Nagata Masato Katahira Source Type: research
Characterization of human XPD helicase activity with Single Molecule Magnetic Tweezers
Biophys J. 2023 Dec 18:S0006-3495(23)04152-8. doi: 10.1016/j.bpj.2023.12.014. Online ahead of print.ABSTRACTXPD helicase is a DNA unwinding enzyme involved in DNA repair. As part of TFIIH, XPD opens a repair bubble in DNA for access by proteins in the nucleotide excision repair pathway. XPD uses the energy from ATP hydrolysis to translocate in the 5' to 3' direction on one strand of duplex DNA, displacing the opposite strand in the process. We used magnetic tweezers assays to measure the double-stranded DNA (dsDNA) unwinding and single-stranded DNA (ssDNA) translocation activities of human XPD in isolation. In our experime...
Source: Biophysical Journal - December 19, 2023 Category: Physics Authors: Chunfeng Mao Maria Mills Source Type: research
Characterization of human XPD helicase activity with Single Molecule Magnetic Tweezers
Biophys J. 2023 Dec 18:S0006-3495(23)04152-8. doi: 10.1016/j.bpj.2023.12.014. Online ahead of print.ABSTRACTXPD helicase is a DNA unwinding enzyme involved in DNA repair. As part of TFIIH, XPD opens a repair bubble in DNA for access by proteins in the nucleotide excision repair pathway. XPD uses the energy from ATP hydrolysis to translocate in the 5' to 3' direction on one strand of duplex DNA, displacing the opposite strand in the process. We used magnetic tweezers assays to measure the double-stranded DNA (dsDNA) unwinding and single-stranded DNA (ssDNA) translocation activities of human XPD in isolation. In our experime...
Source: Biophysical Journal - December 19, 2023 Category: Physics Authors: Chunfeng Mao Maria Mills Source Type: research
Interpreting Molecular Dynamics Forces as Deep Learning Gradients Improves Quality Of Predicted Protein Structures
Biophys J. 2023 Dec 15:S0006-3495(23)04149-8. doi: 10.1016/j.bpj.2023.12.011. Online ahead of print.ABSTRACTProtein structure predictions from deep learning models like AlphaFold2, despite their remarkable accuracy, are likely insufficient for direct use in downstream tasks like molecular docking. The functionality of such models could be improved with a combination of increased accuracy and physical intuition. We propose a new method to train deep learning protein structure prediction models using molecular dynamics force fields to work toward these goals. Our custom PyTorch loss function, OpenMM-Loss, represents the pote...
Source: Biophysical Journal - December 17, 2023 Category: Physics Authors: Jonathan Edward King David Ryan Koes Source Type: research
Interpreting Molecular Dynamics Forces as Deep Learning Gradients Improves Quality Of Predicted Protein Structures
Biophys J. 2023 Dec 15:S0006-3495(23)04149-8. doi: 10.1016/j.bpj.2023.12.011. Online ahead of print.ABSTRACTProtein structure predictions from deep learning models like AlphaFold2, despite their remarkable accuracy, are likely insufficient for direct use in downstream tasks like molecular docking. The functionality of such models could be improved with a combination of increased accuracy and physical intuition. We propose a new method to train deep learning protein structure prediction models using molecular dynamics force fields to work toward these goals. Our custom PyTorch loss function, OpenMM-Loss, represents the pote...
Source: Biophysical Journal - December 17, 2023 Category: Physics Authors: Jonathan Edward King David Ryan Koes Source Type: research
Modeling transcriptional regulation of the cell cycle using a novel cybernetic-inspired approach
Biophys J. 2023 Dec 15:S0006-3495(23)04148-6. doi: 10.1016/j.bpj.2023.12.010. Online ahead of print.ABSTRACTQuantitative understanding of cellular processes, such as cell cycle and differentiation, is impeded by various forms of complexity ranging from myriad molecular players and their multilevel regulatory interactions, cellular evolution with multiple intermediate stages, lack of elucidation of cause-effect relationships among the many system players, and the computational complexity associated with the profusion of variables and parameters. In this paper, we present a modeling framework based on the cybernetic concept ...
Source: Biophysical Journal - December 16, 2023 Category: Physics Authors: Rubesh Raja Sana Khanum Lina Aboulmouna Mano R Maurya Shakti Gupta Shankar Subramaniam Doraiswami Ramkrishna Source Type: research
Computational simulations of Bispecific T-Cell Engagers by a Multiscale Model
Biophys J. 2023 Dec 14:S0006-3495(23)04150-4. doi: 10.1016/j.bpj.2023.12.012. Online ahead of print.ABSTRACTThe use of bispecific antibodies as T cell engagers can bypass the normal TCR-MHC interaction, redirect the cytotoxic activity of T-cells, and lead to highly efficient tumor cell killing. However, this immunotherapy also causes significant on-target off-tumor toxicologic effects, especially when it is used to treat solid tumors. In order to avoid these adverse events, it is necessary to understand the fundamental mechanisms involved in the physical process of T cell engagement. We developed a multiscale computational...
Source: Biophysical Journal - December 16, 2023 Category: Physics Authors: Zhaoqian Su Steven C Almo Yinghao Wu Source Type: research
Modeling transcriptional regulation of the cell cycle using a novel cybernetic-inspired approach
Biophys J. 2023 Dec 15:S0006-3495(23)04148-6. doi: 10.1016/j.bpj.2023.12.010. Online ahead of print.ABSTRACTQuantitative understanding of cellular processes, such as cell cycle and differentiation, is impeded by various forms of complexity ranging from myriad molecular players and their multilevel regulatory interactions, cellular evolution with multiple intermediate stages, lack of elucidation of cause-effect relationships among the many system players, and the computational complexity associated with the profusion of variables and parameters. In this paper, we present a modeling framework based on the cybernetic concept ...
Source: Biophysical Journal - December 16, 2023 Category: Physics Authors: Rubesh Raja Sana Khanum Lina Aboulmouna Mano R Maurya Shakti Gupta Shankar Subramaniam Doraiswami Ramkrishna Source Type: research
