Article
Biochemistry & Molecular Biology
Muthu Kumar Thirunavukkarasu, Ramanathan Karuppasamy
Summary: The study screened a candidate with high binding affinity in MEK protein from a library of 11,808 compounds, and suggested that Nebivolol may be an excellent candidate for MEK inhibition in NSCLC patients in the future.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Chemistry, Medicinal
Yan-jing Sheng, Yue-wen Yin, Yu-qiang Ma, Hong-ming Ding
Summary: Accurate calculation of protein-protein binding free energy is crucial in biological and medical science, and a new strategy involving screened electrostatic energy has been developed in this study to improve the accuracy of calculations. The modified MM/PBSA method shows better correlation and smaller errors compared to the standard method, especially in systems with proteins carrying like charges. This study highlights the potential of the modified MM/PBSA in accurately predicting binding energies in highly charged biosystems.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Engineering, Environmental
Mingna Zheng, Yanwei Li, Weiliang Dong, Shanshan Feng, Qingzhu Zhang, Wenxing Wang
Summary: Four concerted steps are needed to complete the catalytic cycle of PET biotransformation by leaf-branch compost cutinase (LCC), with deacylation identified as the rate-determining step. Unprecedented fluctuations of hydrogen bond length were observed during LCC catalyzed transformation process toward PET, indicating a potential widespread phenomenon in enzymes containing catalytic triads. Possible features influencing the catalytic reaction were identified, establishing correlations between activation energies and key features.
JOURNAL OF HAZARDOUS MATERIALS
(2022)
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
Physics, Multidisciplinary
Yuan-Qiang Chen, Yan-Jing Sheng, Hong-Ming Ding, Yu-Qiang Ma
Summary: The study demonstrated that using screening electrostatic energy in molecular mechanics can greatly improve the performance of MM/PBSA in predicting binding energy, especially in highly charged biological systems. This highlights the potential power of the screening MM/PBSA method for accurately predicting binding affinity.
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
Biochemistry & Molecular Biology
Halise Yalazan, Damla Koc, Fadime Aydin Kose, Seda Fandakli, Burak Tuzun, Muhammed Ismail Akgul, Nastaran Sadeghian, Parham Taslimi, Halit Kantekin
Summary: In this study, new Schiff base compounds derived from chalcone-derived amine compounds containing halogen groups and 4-hydroxybenzaldehyde were synthesized and characterized. The synthesized compounds showed inhibitory activity against Acetylcholinesterase and Butyrylcholinesterase enzymes, as well as potential anticancer activity against neuroblastoma cell lines. Molecular docking and ADME analysis were also conducted to further investigate the properties of the compounds.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
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
Zijian Wang, Qingzhu Zhang, Guoqiang Wang, Wenxing Wang, Qiao Wang
Summary: This study systematically investigated the hydrolysis mechanism of methomyl catalyzed by esterase PestE. The results provided atomic-level details of the mechanism and free energy profiles. Serine-initiated nucleophilic attack was identified as the rate-determining step, and the importance of protein-substrate interactions and key active site residues was elucidated.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Dan Parkin, Mitsunori Takano
Summary: The generalized Born (GB) model is a powerful method for accelerating MD simulations of charged biological molecules in water, and the adjustment of parameters is essential for accurate calculation of the Coulomb energy. This study clarifies that increasing the intrinsic radius rho in the GB model enhances the Coulomb bond stability through the interaction energy term. The use of larger values for the intrinsic radii of hydrogen and oxygen atoms, together with a relatively small value for the spatial integration cutoff, can better reproduce the Coulombic attraction between protein molecules.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biology
Shriram D. Ranade, Shankar G. Alegaon, U. Venkatasubramanian, A. Soundarya Priya, Rohini S. Kavalapure, Jagdish Chand, Sunil S. Jalalpure, D. Vinod
Summary: This study aimed to design, synthesize, and evaluate 4-aminoquinoline hybrid compounds as potential Eg5 inhibitors. Compounds 6c, 6d, 6g, and 6h showed sensitivity to Eg5 inhibition based on data from Malachite green and steady state ATPase assays. Compound 4 and 6c exhibited promising inhibitory activity, with IC50 values of 2.32 ± 0.23 μM and 1.97 ± 0.23 μM, respectively. Molecular docking, MM/GBSA calculations, and molecular dynamic simulations were performed to evaluate the interactions between ligands and the binding site of the kinesin spindle protein, indicating that these 4-aminoquinoline Schiff's base hybrids may be potential candidates for Eg5 inhibitors. Further in-vivo research is needed.
COMPUTATIONAL BIOLOGY AND CHEMISTRY
(2023)
Article
Green & Sustainable Science & Technology
Mingna Zheng, Yanwei Li, Rui Xue, Weiliang Dong, Qingzhu Zhang, Wenxing Wang
Summary: Enzymatic depolymerization is an important method for dealing with PET pollution, but the understanding of depolymerization mechanism of environment-relevant PET waste and the influence of PET size on depolymerization efficiency is still limited. This study used nanosized model substrate to investigate the PET depolymerization process and elucidated the effects of PET size and active site features on activation energy barriers. These findings provide important insights for the development of rational enzyme engineering strategies for environmentally friendly and efficient removal of PET.
JOURNAL OF CLEANER PRODUCTION
(2022)
Article
Biochemistry & Molecular Biology
Sofia D'Souza, S. Balaji, K. Prema
Summary: This study successfully developed new 3CL protease inhibitors using 2D and 3D QSAR models, and validated their inhibitory effects on SARS-CoV through molecular docking and molecular dynamics simulations. The newly designed compounds showed higher interaction energies with active site residues and improved pharmacokinetic properties.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Biochemistry & Molecular Biology
Ahmed Samir, Wael M. Elshemey, Abdo A. Elfiky
Summary: The interaction between the C-terminal domain (CTD) of the polymerase acidic (PA) component of flu A RNA polymerase and heptad repeats from human polymerase II CTD was computationally studied. A unique compound was found to effectively bind to the active site residues in each of the three RdRps, potentially inhibiting the activity of the viruses. This in silico analysis suggests a promising novel lead to block flu A RdRp.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
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
Biochemical Research Methods
Yanan Tian, Xiaorui Wang, Xiaojun Yao, Huanxiang Liu, Ying Yang
Summary: This paper proposes a novel graph neural network, IFGN, which gradually identifies the key atoms/groups in the molecule related to predicted properties by a multistep focus mechanism. It also generates multistep interpretations to provide a deeper understanding of the model's predictive behaviors.
BRIEFINGS IN BIOINFORMATICS
(2023)
Review
Biochemical Research Methods
Yuan-Qin Huang, Ping Sun, Yi Chen, Huan-Xiang Liu, Ge-Fei Hao, Bao-An Song
Summary: Drug resistance is a major issue impacting human health and agriculture. Developing approaches to address target mutation-induced drug resistance is crucial in biological research. Bioinformatics tools have been developed over the past decade to explore this type of drug resistance, offering a cost-effective and efficient means of analysis. However, these tools are underutilized and their strengths and limitations have not been thoroughly evaluated. This study systematically surveyed 59 freely available bioinformatics tools and analyzed their functionality, data volume, source, operating principle, and performance. The study also discussed the strengths, limitations, and application examples of these tools, providing a valuable toolbox for researchers in biomedical, pesticide, bioinformatics, and pharmaceutical engineering fields, as well as a platform for non-specialists to understand drug resistance prediction.
BRIEFINGS IN BIOINFORMATICS
(2023)
Review
Biochemistry & Molecular Biology
Mengrong Li, Yiqiong Bao, Miaomiao Li, Jingjing Guo
Summary: G protein-coupled receptors (GPCRs), as a large superfamily of cell-surface proteins, play crucial roles in cell signaling and regulate various physiological and pathological processes, making them an important source of drug targets. However, due to the challenging dynamic structures of GPCRs, only a few allosteric ligands have been approved as drugs. Fortunately, the development of computational biology provides insights into the mechanism of GPCR allosteric ligands, which is vital for the discovery of new therapeutic agents. This article provides a comprehensive overview of the resources and approaches in computational biology related to GPCR allostery and conformational dynamics, as well as the current limitations and challenges in the field.
CURRENT MEDICINAL CHEMISTRY
(2023)
Article
Cell Biology
Mengrong Li, Yiqiong Bao, Ran Xu, Miaomiao Li, Lili Xi, Jingjing Guo
Summary: The identification and development of non-peptide allosteric modulators for PTH1R have gained attention. It has been found that a negative allosteric modulator (NAM) inhibits the activation of PTH1R, but the mechanism is unclear. Molecular dynamics simulations and analytical approaches reveal that NAM destabilizes the PTH1R-PTH-spep/qpep complexes, weakens PTH/peps-PTH1R binding, and reduces intra- and inter-molecular couplings in PTH1R. Compared with positive allosteric effects induced by extracellular Ca2+, the negative allosteric regulator significantly reduces the correlation between PTH and G-protein binding sites. These findings contribute to the development of new therapeutics for diseases caused by PTH1R abnormal activation.
Article
Biochemistry & Molecular Biology
Fengling Wang, Wenling Ye, Yongxing He, Haiyang Zhong, Yongchang Zhu, Jianting Han, Xiaoqing Gong, Yanan Tian, Yuwei Wang, Shuang Wang, Shaoping Ji, Huanxiang Liu, Xiaojun Yao
Summary: Targeting the PD-1/PD-L1 immunologic checkpoint has provided a breakthrough in cancer therapy. A small molecule inhibitor called CBPA was identified as an effective PD-L1 inhibitor with blocking activity and T-cell reinvigoration capacity. CBPA also showed significant antitumor efficacy in mouse tumor models without observable organ toxicity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Lili Xi, Axi Shi, Tiantian Shen, Guoxu Wang, Yuhui Wei, Jingjing Guo
Summary: Cholestasis is a common clinical disease caused by a disruption in bile acids homeostasis, and the Farnesoid X receptor (FXR) plays a critical role in regulating this balance. This study aimed to identify potential FXR agonists for the treatment of cholestasis using a molecular docking-based virtual screening method. Six compounds were selected and evaluated, with licraside showing the most promising results. In vivo evaluation using an animal model confirmed that licraside reduced biliary and serum markers of cholestasis and had a therapeutic effect on liver injury. These findings highlight the potential of licraside as an FXR agonist for cholestasis treatment, and the study contributes valuable insights into the development of novel compounds from traditional Chinese medicine.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Ran Xu, Yiqiong Bao, Mengrong Li, Yan Zhang, Lili Xi, Jingjing Guo
Summary: In this study, computational approaches were used to investigate the molecular mechanisms behind the improved activity of a phthalate-degrading enzyme with three distal mutations. The mutations caused changes in the enzyme's conformational states and key functional regions, facilitating substrate binding and catalytic efficiency. Furthermore, the introduction of a distal disulfide bond improved the thermostability of the enzyme. Overall, this work provides insights into the rational design of esterases for industrial applications.
Article
Biochemistry & Molecular Biology
Jian Ma, Jingjing Guo, Zhiwei Fan, Weiling Zhao, Xiaobo Zhou
Summary: In this study, a tool called CVAM was developed to infer the CNA profile from spatial transcriptome data, which performed better in identifying CNA events compared to existing tools. Co-occurrence and mutual exclusion between CNA events in tumor clusters were also analyzed, providing insights into potential interactions between mutated genes. Additionally, Ripley's K-function was applied for CNA multi-distance spatial pattern analysis to understand the spatial distribution differences of different gene CNA events, enabling more effective treatment measures based on spatial characteristics of genes.
Article
Biochemical Research Methods
Yang Yue, Shu Li, Lingling Wang, Huanxiang Liu, Henry H. Y. Tong, Shan He
Summary: In this study, a novel framework called MpbPPI is proposed for accurate prediction of amino acid mutations on protein-protein interactions. Pre-training on a strictly screened dataset enables MpbPPI to generate high-quality representations and support flexible application on different mutant-type protein-protein complexes.
BRIEFINGS IN BIOINFORMATICS
(2023)
Article
Biochemistry & Molecular Biology
Yunhao Ma, Hongmei Zhu, Xinrong Jiang, Zhongkun Zhou, Yong Zhou, Yanan Tian, Hao Zhang, Mengze Sun, Lixue Tu, Juan Lu, Yuqing Niu, Huanxiang Liu, Yingqian Liu, Peng Chen
Summary: This study evaluated the cytotoxicity of 8-methoxy-2,5-dimethyl-5H-indolo[2,3-b]quinoline (MMNC) in colorectal cancer cells and found that MMNC exerted cytotoxicity by inhibiting the expression of PI3K/AKT/mTOR signaling pathway-related proteins, inhibiting cell proliferation, blocking the cell cycle, and inducing apoptosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Zhe Wang, Haiyang Zhong, Jintu Zhang, Peichen Pan, Dong Wang, Huanxiang Liu, Xiaojun Yao, Tingjun Hou, Yu Kang
Summary: This study systematically evaluates the performance of traditional methods and AI models in small-molecule conformer generation. The results show that traditional methods outperform AI models in reproducing bioactive conformations, while an AI model has an advantage in generating low-energy conformations.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Chemistry, Medicinal
Jieyu Jin, Dong Wang, Guqin Shi, Jingxiao Bao, Jike Wang, Haotian Zhang, Peichen Pan, Dan Li, Xiaojun Yao, Huanxiang Liu, Tingjun Hou, Yu Kang
Summary: Recently, deep generative models, such as FFLOM, have shown promise in fragment-based drug design by generating molecules with desired properties. FFLOM achieves state-of-the-art performance in terms of validity, uniqueness, novelty, and recovery of generated molecules. It also demonstrates excellent potential in practical scenarios including fragment linking, PROTAC design, R-group growing, and R-group optimization, generating molecules with novel fragments and higher binding affinity.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Computer Science, Artificial Intelligence
Chao Liu, Lei Wu, Wensheng Xiao, Guangxin Li, Dengpan Xu, Jingjing Guo, Wentao Li
Summary: In this study, a novel variant of ant colony optimization algorithm called improved heuristic mechanism ACO (IHMACO) is proposed. It contains four improved mechanisms to enhance the efficiency and effectiveness of path planning. Experimental results show that IHMACO outperforms existing approaches in terms of path turn times.
KNOWLEDGE-BASED SYSTEMS
(2023)
Article
Agronomy
Yiqiong Bao, Yan Xu, Fangying Jia, Mengrong Li, Ran Xu, Feng Zhang, Jingjing Guo
Summary: This study used multiple computational approaches to elucidate the allosteric inhibition mechanism of Phenamacril (PHA) on Myosin I (FgMyoI) from Fusarium graminearum. The results showed that PHA binding increased the ATP binding affinity, which hindered the release of hydrolysis products. Simulations also revealed changes in the actin-binding interface and signaling transduction, disrupting the actomyosin cycle and reducing motor force generation. Experimental results confirmed that PHA reduced the enzymatic activity of myosin and its binding with actin. Overall, this study provides new insights into myosin allostery and offers opportunities for drug/fungicide discovery targeting myosin.
PEST MANAGEMENT SCIENCE
(2023)
Review
Chemistry, Multidisciplinary
Jingjing Guo, Yiqiong Bao, Mengrong Li, Shu Li, Lili Xi, Pengyang Xin, Lei Wu, Huanxiang Liu, Yuguang Mu
Summary: Biological membranes are complex structures vital for life. Experimental investigation of biomembranes is challenging, but computational approaches such as molecular dynamics (MD) simulations have provided insights into their atomic details and cellular functions. This review highlights the latest advancements in computational methods, from force fields to MD simulations and trajectory analysis. It also discusses current research topics, challenges, and future directions for applying computational technologies in biomembrane systems.
WILEY INTERDISCIPLINARY REVIEWS-COMPUTATIONAL MOLECULAR SCIENCE
(2023)
