Review
Biochemistry & Molecular Biology
Fang-Yuan Teng, Zong-Zhe Jiang, Man Guo, Xiao-Zhen Tan, Feng Chen, Xu-Guang Xi, Yong Xu
Summary: G-quadruplex (G4) DNA is a unique DNA structure found in various diseases and considered a potential target for drug design. This review provides an overview of the detection methods, structure, and functions of G4 DNA, as well as some drug design strategies targeting G4.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Chemistry, Physical
Yuqi Yu, Arnau Rue Casamajo, William Finnigan, Christian Schnepel, Rhys Barker, Charlotte Morrill, Rachel S. Heath, Leonardo De Maria, Nicholas J. Turner, Nigel S. Scrutton
Summary: Biocatalysis plays a crucial role in the discovery, development, and manufacturing of pharmaceuticals. A structure-based computational workflow called IREDFisher has been developed to prioritize protein sequences based on predicted activities, reducing the need for resource-intensive laboratory-based screening. IREDFisher successfully identified highly active imine reductases for various reactions, significantly reducing the number of samples that need to be tested in vitro. With a user-friendly web interface, IREDFisher enables rapid discovery of biocatalysts with minimal time and resource expenditure.
Article
Biochemistry & Molecular Biology
Banesh Sooram, Uppuladinne Mallikarjunachari, Sonavane Uddavesh, Prakash Saudagar
Summary: This study used a pharmacophore-guided approach to design a drug candidate targeting Leishmania N-Myristoyl transferase (LdNMT). By substituting alanine in pharmacophoric residues, the affinity of myristate with NMT was elevated. The compound 4UL was found to be highly specific towards leishmanial NMT, suggesting it is a strong leishmanial NMT inhibitor.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Multidisciplinary Sciences
Longxing Cao, Brian Coventry, Inna Goreshnik, Buwei Huang, William Sheffler, Joon Sung Park, Kevin M. Jude, Iva Markovic, Rameshwar U. Kadam, Koen H. G. Verschueren, Kenneth Verstraete, Scott Thomas Russell Walsh, Nathaniel Bennett, Ashish Phal, Aerin Yang, Lisa Kozodoy, Michelle DeWitt, Lora Picton, Lauren Miller, Eva-Maria Strauch, Nicholas D. DeBouver, Allison Pires, Asim K. Bera, Samer Halabiya, Bradley Hammerson, Wei Yang, Steffen Bernard, Lance Stewart, Ian A. Wilson, Hannele Ruohola-Baker, Joseph Schlessinger, Sangwon Lee, Savvas N. Savvides, K. Christopher Garcia, David Baker
Summary: This study presents a general solution to the challenge of designing proteins that can bind to specific sites on the surface of a target protein solely based on its three-dimensional structure. Through experimental validation, the method demonstrates broad applicability and successful de novo design of binding proteins for diverse protein targets. Detailed feedback from extensive experimental data guides improvements in both the method and our understanding of protein-protein interactions.
Article
Chemistry, Medicinal
Giuseppe Lamanna, Pietro Delre, Gilles Marcou, Michele Saviano, Alexandre Varnek, Dragos Horvath, Giuseppe Felice Mangiatordi
Summary: This study introduces a new de novo design algorithm called GENERA that combines the capabilities of a deep-learning algorithm for automated drug-like analogue design, called DeLA-Drug, with a genetic algorithm for generating molecules with desired target-oriented properties. GENERA was applied to the angiotensin-converting enzyme 2 (ACE2) target, and its ability to de novo design promising candidates was assessed using docking programs PLANTS and GLIDE. The study demonstrates that GENERA can effectively perform multiobjective optimization and generate focused libraries with better scores compared to a starting set of known ACE-2 binders.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Oncology
Parisa Bakhshi, Maryam Nourizadeh, Laleh Sharifi, Mohammad M. Farajollahi, Monireh Mohsenzadegan
Summary: The study demonstrated the potent ability of antigen-pulsed DCs to stimulate T cell expansion, and the induced CTLs showed significant cytotoxicity against target cells.
CANCER CELL INTERNATIONAL
(2023)
Article
Multidisciplinary Sciences
Erika Davidoff Aguas, Abdul-Rahman Azizogli, Jatin Kashyap, Joseph Dodd-o, Zain Siddiqui, Jay Sy, Vivek Kumar
Summary: Chronic inflammation can lead to autoimmune diseases like rheumatoid arthritis and atherosclerosis. CCL2, also known as MCP-1, plays a crucial role in the progression of these diseases by attracting monocytes to the site of injury and promoting inflammation. In this study, computational modeling techniques were used to design high-affinity peptide binders for CCL2, with the aim of preventing its binding to CCR2 and reducing inflammation. Further analysis and experiments are needed to validate the accuracy of this computational approach in designing CCL2 cytokine binders.
ADVANCED THEORY AND SIMULATIONS
(2023)
Article
Green & Sustainable Science & Technology
Jiangong Li, Xinlei Wang, Harrison Hyung Min Kim, Richard S. Gates, Kaiying Wang
Summary: The negative impact of animal waste on the environment is a significant challenge in livestock production. A novel modeling approach (ATC) is presented in this project to optimize the design and operation of a swine manure management system by formulating economic, engineering, and environmental objectives into individual tasks. This approach simplifies systematic problem formulation and integrates professional assessment models for optimal design.
JOURNAL OF CLEANER PRODUCTION
(2021)
Article
Pharmacology & Pharmacy
Chenyu Zhang, Xiang Li, Zhenjian Xing, Honglan Zhong, Dianbao Yu, Rui Yu, Xin Deng
Summary: In this study, an anticancer AMP (Mastoparan) and its derivatives were designed and evaluated. Preliminary studies showed that the Mastoparan analogue KM8 exhibited selective antitumor effects but had metabolic instability. By substituting the 9Ala residue in KM8, a long-acting derivative KM8-Aib was generated, which showed higher metabolic stability, potent anticancer activity, and lower toxicity. Therefore, KM8-Aib is suggested as a potential antimalignant agent for further study.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2023)
Article
Chemistry, Multidisciplinary
Hao Ruan, Chen Yu, Xiaogang Niu, Weilin Zhang, Hanzhong Liu, Limin Chen, Ruoyao Xiong, Qi Sun, Changwen Jin, Ying Liu, Luhua Lai
Summary: In this study, a hierarchical computational strategy for IDP drug discovery was proposed and successfully applied to identify two compounds that bind p53 TAD1 and restore wild-type p53 function. The study demonstrates the efficiency of IDPDVS in IDP drug discovery and the potential for direct targeting of p53 TAD1 by small molecules.
Article
Geochemistry & Geophysics
Sixue Wu, Dirk J. Verschuur, Gerrit Blacquiere
Summary: Imperfect spatial sampling in seismic exploration methods results in a lack of illumination at the target in the subsurface, impacting reservoir monitoring and production. This study develops a methodology that automatically optimizes an irregular receiver geometry to improve image resolution and angle-dependent illumination information.
IEEE TRANSACTIONS ON GEOSCIENCE AND REMOTE SENSING
(2022)
Article
Multidisciplinary Sciences
Ran Li, Yimei Wang, Jie Du, Xiangyu Wang, Ailin Duan, Ruifang Gao, Junyu Liu, Bing Li
Summary: In this study, nanoscale graphene oxide (NGO) was successfully used as a drug carrier to improve the process of tumor-targeted drug releases and enhance the accumulation of chemotherapy drugs in tumor tissues while reducing toxicity to normal cells. The designed nanoparticle system DOX@NGO-PEG-HN-1 showed significantly increased cellular uptake and cytotoxicity in oral squamous cell carcinoma cells, with pH-responsive drug release capabilities, demonstrating potential for improving anticancer drug efficiency.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Ruifang Li, Jiasha Wu, Fuyang He, Qingpeng Xu, Kedong Yin, Shang Li, Weitong Li, Ao Wei, Lan Zhang, Xin-Hui Zhang, Beibei Zhang
Summary: Researchers designed a set of CGA-N12 analogues that showed stronger antifungal activity compared to the original compound CGA-N12. These analogues were able to kill invasive Candida species and their persist cells, as well as inhibit biofilm formation and eradicate preformed biofilms.
BIOORGANIC CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Robert L. Jernigan, Kannan Sankar, Kejue Jia, Eshel Faraggi, Andrzej Kloczkowski
Summary: Two new computational approaches have been described for designing peptide-based drugs, which emphasize the importance of structural variability in the binding process, especially for disordered proteins. The design process should be less restrictive to allow for the potential effectiveness of multiple inhibitors.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Gabriele La Monica, Antonino Lauria, Alessia Bono, Annamaria Martorana
Summary: The approval of HIV-1 protease inhibitors marked an important step in AIDS treatment, but also led to severe side effects. In-silico techniques can help design new selective inhibitors with well-fitting selectivity and without undesirable interactions. This new method could be a reliable tool in the research of targeted small molecules.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)