Article
Biochemistry & Molecular Biology
Guangfeng Shao, Jingxiao Bao, Xiaolin Pan, Xiao He, Yifei Qi, John Z. H. Zhang
Summary: The study analyzed the complex structures of AR ligand-binding domain with fifteen ligands using molecular dynamics simulations and ASIE method, quantitatively identifying hotspot residues which are predominantly hydrophobic. The calculation showed good correlation between total binding free energies obtained and experimental data, providing important insight for the design of future inhibitors.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Wen Wei, Huang Dading, Bao Jingxiao, John Z. H. Zhang
Summary: Molecular dynamics simulations were conducted on two PD-1/monoclonal antibody complexes, pembrolizumab and nivolumab, revealing different binding mechanisms. Both complexes share (PD-1)K131 as a binding hotspot, dominated by van der Waals energy. Improving the contributions of electrostatic energy may enhance the efficiency of monoclonal antibodies binding to PD-1.
CHEMICAL JOURNAL OF CHINESE UNIVERSITIES-CHINESE
(2021)
Article
Chemistry, Physical
Yuxi Lv, Song Luo, Kaifang Huang, Han Wang, Shuheng Dong, Yalong Cong, John Z. H. Zhang, Lili Duan
Summary: This study investigated the effect of bridging water on the binding of neuraminidase and two ligands, showing that the presence of bridging water enhances the stability and binding free energy of the complex. The study identified key residues in the neuraminidase-ligand complex and demonstrated that bridging water can regulate the hydrogen bond network to increase the number of hydrogen bonds, contributing to the stability of the complex and promoting binding.
JOURNAL OF MOLECULAR LIQUIDS
(2021)
Article
Biochemistry & Molecular Biology
Shuaizhen Tian, Changge Ji, John Z. H. Zhang
Summary: This study investigates the protein-peptide interaction between the BIR3 and BIR2 domains of XIAP and the SMAC peptide using molecular dynamics simulations and alanine scanning calculations. Energetic contribution of each binding residue and identification of hotspots reveal the importance of electrostatic polarization in stabilizing the protein-protein complex structure. By using polarized protein-specific charges, better agreement with experimental results is achieved for calculated binding free energies.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Biochemistry & Molecular Biology
Wei Xia, Liping He, Jingxiao Bao, Yifei Qi, John Z. H. Zhang
Summary: Targeting the immunological checkpoint PD-1/PD-L1 with antibodies has shown potential in improving cancer treatment, but comes with drawbacks such as high cost and low patient tolerance. The development of small-molecule PD-1/PD-L1 inhibitors is slow due to challenges like poor pharmacodynamic properties. Recent discoveries of compounds binding the PD-L1/PD-L1 dimer interface offer an alternative approach to inhibit PD-1/PD-L1 interaction efficiently.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Chemistry, Multidisciplinary
Y. X. Yu, W. T. Liu, H. Y. Li, W. Wang, H. B. Sun, L. L. Zhang, S. L. Wu
Summary: The HIV-1 protease (PR) is considered an efficient target for anti-AIDS drug design. Molecular dynamics simulations and post-processing analysis were used to study the binding mechanism of three drugs (LPV, NFV, ATV) to the PR. The results show that the drugs affect the structural flexibility and dynamics behavior of PR, with common interaction clusters, indicating potential targets for clinically available inhibitors.
SAR AND QSAR IN ENVIRONMENTAL RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Yalong Cong, Lili Duan, Kaifang Huang, Jinxiao Bao, John Z. H. Zhang
Summary: In this study, binding free energies between two HIV proteases and inhibitors were calculated using the IE method, revealing common hot-spot residues and differences in residue contributions between HIV-1 and HIV-2, explaining variations in inhibitor potency. The research provides quantitative insights into HIV-inhibitor binding mechanisms and offers theoretical guidance for designing equipotent HIV-1/HIV-2 protease inhibitors.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Biochemistry & Molecular Biology
Trupti S. Chitre, Purvaj V. Hirode, Deepak K. Lokwani, Aniket L. Bhatambrekar, Sayli G. Hajare, Shubhangi B. Thorat, D. Priya, Kunal B. Pradhan, Kalyani D. Asgaonkar, Shirish P. Jain
Summary: A significant three descriptor QSAR model was established to predict the Hec1/Nek2 inhibitory activity of 2-aminothiazoles derivatives, based on which new lead molecules were designed and further studied through ADMET and molecular docking. The study provides insights into the key interactions between the derivatives and Hec1/Nek2 protein, facilitating the development of potential anticancer molecules.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Chemistry, Medicinal
Rory M. Crean, Christopher R. Pudney, David K. Cole, Marc W. van der Kamp
Summary: The study proposes a reliable protocol for evaluating the binding of T-cell receptor variants to target proteins, which can be efficiently applied to protein design with applications in biological therapeutics.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Chemistry, Physical
Lili Duan, Shuheng Dong, Kaifang Huang, Yalong Cong, Song Luo, John Z. H. Zhang
Summary: In this study, computational analysis was used to investigate the protein-protein interactions between Bcl-xL/Bcl-2 and Bad/Bax, revealing that the Bcl-xL/Bad complex has more hot-spot residues and stronger binding affinity.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2021)
Article
Biochemistry & Molecular Biology
Mohsen Sargolzaei, Hossein Nikoofard
Summary: In this study, we designed a suitable ester prodrug of omapatrilat for CNS diseases by considering its ability to penetrate the blood-brain barrier. The most potent stereoisomers against brain carboxylesterase were determined through molecular docking and homology modeling. Molecular dynamics simulation and structural analysis were performed to confirm the suitability of the prodrug structure for crossing the blood-brain barrier and binding to brain carboxylesterase. Additionally, the QM/MM calculation revealed the catalytic reaction mechanism of the prodrug against brain carboxylesterase.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Physics, Atomic, Molecular & Chemical
Song Luo, Xiaoyu Zhao, Yihui Wang, Lili Duan
Summary: The study investigated the drug resistance mechanism caused by mutations in subtype N9 (A/H7N9) of Influenza A, revealing that the mutation led to the disruption of the hydrogen bonding network, weakening the drug binding ability and potentially promoting resistance. This study could provide insights for the development of novel drug delivery strategies in treating A/HxN9 with drug-resistant mutations.
CHINESE JOURNAL OF CHEMICAL PHYSICS
(2021)
Article
Chemistry, Multidisciplinary
Song Luo, Kaifang Huang, Xiaoyu Zhao, Yalong Cong, John Z. H. Zhang, Lili Duan
Summary: The study found that ritonavir, arbidol, and chloroquine exhibited outstanding binding ability to monomeric M-pro, while chloroquine may not effectively inhibit the activity of M-pro. Hot-spot residues Met165, Hie41, and Gln189 play important roles in binding to monomeric M-pro, while Gln189 and Met165 may be the focus in the discovery and development of anti-COVID-19 drugs in dimeric M-pro systems.
Article
Oncology
Hassan Hussain Almasoudi, Mohammed Ageeli Hakami, Abdulfattah Y. Alhazmi, Mohammed Makkawi, Sultan Alasmari, Youssef Saeed Alghamdi, Mutaib M. Mashraqi
Summary: Cervical cancer is a major cause of illness and death among women worldwide. Drug resistance and side effects are significant challenges in its treatment. Therefore, repurposing existing drugs to target multiple sites in cervical cancer is an attractive approach. In this study, taxifolin, a flavonoid with antioxidant and anti-inflammatory properties, was identified as a potential multitargeted therapy for cervical cancer through extensive screening and computational analysis.
Article
Chemistry, Physical
Tom Reichert, Marija Vucicevic, Paula Hillman, Marcus Bleicher, Sanja J. Armakovic, Stevan Armakovic
Summary: This study used DFT and SAPT calculations, along with MD simulations, to investigate the interaction between a sumanene molecule and 5-fluorouracil (5-FU). The results showed that 5-FU binds more strongly to the concave side of sumanene. Different geometric shapes of sumanene also influenced the interaction between sumanene and 5-FU.
JOURNAL OF MOLECULAR LIQUIDS
(2021)