Article
Biochemistry & Molecular Biology
S. M. Esther Rubavathy, Kandhan Palanisamy, S. Priyankha, Ramasamy Thilagavathi, Muthuramalingam Prakash, Chelliah Selvam
Summary: In this study, HDAC8 inhibitors with high affinity and good ADMET characteristics were screened from a natural product database. Through molecular docking, molecular dynamics, and MM-PBSA analysis, it was found that these compounds have strong binding affinity and are more effective than romidepsin. These findings may contribute to further development of HDAC8 inhibitors.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Chemistry, Multidisciplinary
Anbarasu Krishnan, Duraisami Dhamodharan, Thanigaivel Sundaram, Vickram Sundaram, Hun-Soo Byun
Summary: In this computational study, virtual screening was conducted on human LMTK3 to identify potential anticancer compounds for the treatment of ER alpha positive breast cancer. The results revealed that the compound NCI26194, screened from the NCI database, has the potential to act as a key drug molecule for this type of breast cancer.
KOREAN JOURNAL OF CHEMICAL ENGINEERING
(2022)
Article
Biochemistry & Molecular Biology
Duc Hoang Lande, Abed Nasereddin, Arne Alder, Tim W. Gilberger, Ron Dzikowski, Johann Gruenefeld, Conrad Kunick
Summary: Malaria is a dangerous infectious disease for which novel antiplasmodial agents are needed due to parasite resistance. N-unsubstituted bisindolylcyclobutenediones were designed as potential drugs and showed promising antiplasmodial activity through molecular docking and synthesis.
Article
Biochemistry & Molecular Biology
Marko Jukic, Rodolphe Auger, Victor Folcher, Matic Proj, Helene Barreteau, Stanislav Gobec, Thierry Touze
Summary: The study identified small molecules that inhibit the activity of BacA, an enzyme involved in the recycling of undecaprenyl pyrophosphate. The compounds showed significant inhibition of the enzyme's activity and also demonstrated antibacterial activity against Escherichia coli strains.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Article
Chemistry, Physical
Matthew Bain, Jose L. Godinez Castellanos, Stephen E. Bradforth
Summary: High-repetition-rate lasers have the potential to revolutionize ultrafast spectroscopy by enabling routine analysis for machine learning models in the design of photochemical syntheses. In this study, we combine innovations in line scan cameras and micro-electro-mechanical grating modulators with high-pressure liquid chromatography pumps to develop a transient absorption spectrometer that can characterize photoreactions in minutes. Additionally, we demonstrate the utility of this technique in exploring the effects of conformational modification on excited-state processes.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2023)
Article
Multidisciplinary Sciences
Bakary N'tji Diallo, Tarryn Swart, Heinrich C. Hoppe, Oezlem Tastan Bishop, Kevin Lobb
Summary: Malaria elimination can benefit from time and cost-efficient approaches for antimalarials, such as drug repurposing. In this study, 25 potential antimalarials were identified from 796 compounds, with 4 showing activity in in vitro testing.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Varshita Srivastava, Biswajit Naik, Priya Godara, Dorothy Das, Venkata Satish Kumar Mattaparthi, Dhaneswar Prusty
Summary: According to CDC, there have been 42,954 confirmed cases of Monkeypox Virus in 94 countries as of August 23. The current treatment relies on repurposed FDA-approved drugs as there are no specific drugs for Monkeypox. A recent study indicates that the Monkeypox outbreak is caused by a unique mutation, which may lead to drug resistance. However, through virtual screening, 15 FDA-approved drugs that can target three viral proteins have been identified, suggesting potential for the development of an effective therapy.
MOLECULAR DIVERSITY
(2023)
Article
Chemistry, Multidisciplinary
E. M. Elamin, S. E. Eshage, S. M. Mohmmode, R. M. Mukhtar, M. Mahjoub, E. Sadelin, T. H. Shoaib, A. Edris, E. M. Elshamly, A. A. Makki, A. Ashour, A. E. Sherif, W. Osman, S. R. M. Ibrahim, G. A. Mohamed, A. A. Alzain
Summary: The objective of this study was to identify new natural compounds that can target two enzymes in the Plasmodium falciparum parasite, which causes malaria. Through e-pharmacophore modelling and molecular docking, nine potential compounds were found to inhibit these enzymes. Further calculations and analysis revealed that three of these compounds have potential as dual-target inhibitors for malaria treatment.
SAR AND QSAR IN ENVIRONMENTAL RESEARCH
(2023)
Article
Immunology
Manoj Kumar Yadav, Manish Kumar Tripathi, Srishti Yadav
Summary: Plasmodium knowlesi, the least studied malaria parasite in Southeast Asia, is characterized as a significant cause of morbidity and mortality. This study identifies PkDHFR as a drug target and explores inhibitors to combat resistance, providing potential candidates for treating P. knowlesi malaria.
MICROBIAL PATHOGENESIS
(2021)
Review
Biochemistry & Molecular Biology
Clara Blanes-Mira, Pilar Fernandez-Aguado, Jorge De Andres-Lopez, Asia Fernandez-Carvajal, Antonio Ferrer-Montiel, Gregorio Fernandez-Ballester
Summary: The rapid advances in 3D techniques and computational methods have led to the identification of highly active compounds in computer drug design. Molecular docking is widely used in virtual screening to filter potential ligands targeted to proteins. Consensus scoring methods improve virtual screening outcomes by averaging the rank or score of individual molecules obtained from different docking programs.
Article
Chemistry, Physical
Phuong Thuy Viet Nguyen, Giang Le Tra Nguyen, Oanh Thi Dinh, Cuong Quoc Duong, Lam H. Nguyen, Thanh N. Truong
Summary: Selecting suitable drug targets is crucial in drug discovery. This study used a combination of druggability filtering, molecular docking, and molecular dynamics simulations to select suitable targets for dengue and malaria. The study identified druggable targets and performed molecular docking and MD simulations to evaluate their binding affinities. The results identified specific targets for further drug design studies.
JOURNAL OF MOLECULAR STRUCTURE
(2022)
Article
Chemistry, Physical
Qiushuang Gao, Peng Yao, Ying Wang, Qizheng Yao, Ji Zhang
Summary: In this study, in silico simulations and drug repurposing approaches were used to identify promising HDAC2 inhibitors. Compounds DB08464, DB00731, DB13930, and DB13696 showed stable binding to HDAC2 and favorable interactions. Additionally, one of the screened compounds, the antiviral drug DB13696, exhibited significant anti-proliferative activity on HepG2 cells with high HDAC2 expression.
JOURNAL OF MOLECULAR STRUCTURE
(2022)
Article
Biochemistry & Molecular Biology
Janet Sabina Xavier, Karthikeyan Jayabalan, V Ragavendran, Muthu Tamizh Manoharan, A. Nityananda Shetty
Summary: A novel class of aroylhydrazones with anticancer properties has been identified through tubulin inhibition studies and anticancer activity tests, with the methyl substituted hydrazone MH-2 showing the strongest anticancer activity. The methyl group is responsible for the effective binding to the protein, making these compounds potential agents in cancer therapy.
BIOORGANIC CHEMISTRY
(2021)
Article
Medicine, Research & Experimental
Mahmoud Ganji, Shohreh Bakhshi, Alireza Shoari, Reza Ahangari Cohan
Summary: This study utilized pharmacophore and QSAR modeling to identify five potential FGFR3 inhibitors for bladder cancer treatment, which showed promising therapeutic properties and low toxicity levels.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Faisal Ahmad, Aqel Albutti, Muhammad Hamza Tariq, Ghufranud Din, Muhammad Tahir ul Qamar, Sajjad Ahmad
Summary: This study used a Computer Aided Drug Discovery approach to identify potential therapeutic agents against Hendra virus (HeV). Two compounds were found to have stable properties and the ability to interfere with the virus. However, further in vitro and in vivo experiments are needed to validate these findings.
Article
Chemistry, Medicinal
Guido Todde, Ran Friedman
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2020)
Article
Biochemistry & Molecular Biology
F. Houshmand, R. Friedman, S. Jalili, J. Schofield
JOURNAL OF MOLECULAR MODELING
(2020)
Article
Biochemical Research Methods
H. Jonathan G. Lindstrom, Ran Friedman
BMC BIOINFORMATICS
(2020)
Article
Chemistry, Physical
Ran Friedman
Summary: Methanol dehydrogenase (MDH) is an enzyme used by certain bacteria for the oxidation of methanol to formaldehyde, with a lanthanide-dependent version having higher affinity for binding Ln(3+) ions than calcium ions due to stronger electrostatic and polarization contributions. Energy decomposition analysis revealed that heavier lanthanides, particularly Gd3+, showed the highest affinity for MDH among the Ln(3+) ions tested.
JOURNAL OF PHYSICAL CHEMISTRY B
(2021)
Article
Oncology
Jingmei Yang, H. Jonathan G. Lindstrom, Ran Friedman
Summary: AML patients may not benefit from a quizartinib/pexidartinib rotation protocol, as demonstrated in cell line studies. Computational modeling suggests that developing specific FLT3 inhibitors less sensitive to resistance mutations might lead to better outcomes in the future. Rotation between drugs with different resistance mutation landscapes may not be effective in postponing resistance emergence.
CANCER CELL INTERNATIONAL
(2021)
Article
Chemistry, Physical
Yuan Xu, Ran Friedman, Wei Wu, Peifeng Su
Summary: DFTB-EDA is a novel energy decomposition analysis scheme based on the DFTB/TD-DFTB method, capable of analyzing interactions in large molecular systems with high efficiency, including intermolecular interactions and non-covalent bonding. Test calculations have demonstrated the efficiency, usefulness, and capabilities of DFTB-EDA.
JOURNAL OF CHEMICAL PHYSICS
(2021)
Review
Chemistry, Multidisciplinary
Ran Friedman
Summary: This article focuses on computational tools available for calculating protein-drug binding affinity changes upon mutations, including free energy calculations, analysis of molecular dynamics simulations, and methods involving quantum mechanical calculations. It also provides a brief overview of experimental methods and observables, along with examples of computational studies that go beyond calculating Gibbs energy changes. Factors to be considered by computational chemists and potential pitfalls are discussed in detail.
WILEY INTERDISCIPLINARY REVIEWS-COMPUTATIONAL MOLECULAR SCIENCE
(2022)
Review
Biochemistry & Molecular Biology
Ran Friedman
Summary: Acute myeloid leukemia (AML) is an aggressive cancer associated with FLT3 gene mutations. Recent studies on the molecular mechanism of FLT3 protein activation suggest that differences in mutation sequences and locations may be related to prognosis. Additionally, the development of new inhibitors should consider drug resistance and the potential of combination therapy.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2022)
Article
Chemistry, Physical
Baswanth Oruganti, Ran Friedman
Summary: Recent research has successfully used wT-metaD simulations and path collective variables (CVs) to explore conformational transitions in protein kinases and other systems. A new approach coupling essential dynamics sampling with wT-metaD simulations was developed to automate path generation for studying activation mechanisms and accurately calculating associated barriers. This study demonstrates the usability of essential dynamics sampling as a path CV in wT-metaD to conveniently study conformational transitions and accurately calculate associated barriers.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2021)
Article
Multidisciplinary Sciences
H. Jonathan G. Lindstrom, Ran Friedman
Summary: Targeted therapies for CML are effective but rarely curative. Drug resistance is a major cause of death in CML, and preventing resistance is crucial. Drug rotation has been theorized as a way to delay resistance, and in vitro testing has shown some promising results in a CML cell line.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Baswanth Oruganti, Erik Lindahl, Jingmei Yang, Wahid Amiri, Rezwan Rahimullah, Ran Friedman
Summary: This study explores the effectiveness of combination therapies using the recently developed allosteric inhibitor asciminib with the ATP-competitive inhibitors nilotinib and dasatinib in inhibiting the BCR-Abl1 kinase activity in CML cell lines. The results show that asciminib significantly enhances the inhibitory activity of nilotinib, but not of dasatinib.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Chemistry, Physical
Yuan Xu, Shu Zhang, Erik Lindahl, Ran Friedman, Wei Wu, Peifeng Su
Summary: In this work, a general tight-binding based energy decomposition analysis (EDA) scheme is proposed for intermolecular interactions. The scheme, known as DFTB-EDA, is capable of performing interaction analysis with different self-consistent charge (SCC) type DFTB methods. By dividing the total interaction energy into frozen, polarization, and dispersion terms, the performance of DFTB-EDA with SCC-DFTB2/3 and GFN1/2-xTB for various interaction systems is discussed and assessed.
JOURNAL OF CHEMICAL PHYSICS
(2022)
Article
Multidisciplinary Sciences
Luisa Moretto, Marko Usaj, Oleg Matusovsky, Dilson E. Rassier, Ran Friedman, Alf Mansson
Summary: Release of Pi from the myosin active site is essential for force generation, but the mechanism behind it is not well understood. This study presents evidence for a multistep Pi-release model that reconciles conflicting views and reveals potential functional complexities.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Physical
Ran Friedman
Summary: The use of actinides for medical, scientific and technological purposes is gaining importance. Understanding their interactions with biomolecules and designing agents with high affinities require accurate reference values for actinide hydration. This study developed a set of ionic radii that enables calculations of binding energies for actinides and biomolecules.
Article
Chemistry, Physical
Thales Souza Freire, Ignez Caracelli, Julio Zukerman-Schpector, Ran Friedman
Summary: Gilteritinib is effective in treatment of acute myeloid leukaemia (AML) by inhibiting the FLT3/ITD mutated protein. However, tumour cells develop resistance to gilteritinib due to mutations in the drug target. We used a computer-aided approach to understand the resistance mechanism and found that the mutations F691L and D698N lead to higher activation energy barrier, making mutant enzymes more active. This suggests that tyrosine kinases contribute to resistance against type 1 and type 2 kinase inhibitors.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2023)