Article
Biochemistry & Molecular Biology
Md. Imtaiyaz Hassan, Darakshan Anjum, Taj Mohammad, Manzar Alam, Mohd Shahnawaz Khan, Moyad Shahwan, Anas Shamsi, Dharmendra Kumar Yadav
Summary: Tyrosine-protein kinase Lyn (LynK) has been identified as a promising therapeutic target for cancer and diabetes. In this study, the researchers used a virtual screening process to discover two natural compounds, Glabrene and Lactupicrin, with high affinity and specificity for LynK. These compounds interact with the ATP-binding pocket of LynK and exhibit drug-like properties, as demonstrated by molecular dynamics simulation.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Chemistry, Physical
Mohsen Yazdani, Ameneh Jafari, Soodeh Mahdian, Mohsen Namazi, Sajjad Gharaghani
Summary: The lack of effective treatment for the current coronavirus family pan-demic, particularly COVID-19, has created the need to identify potential inhibitor candidates to disrupt the binding of the virus to host cells. This study proposes a computational screening method to identify such inhibitors, with the compound PubChem-84280085 identified as a potential candidate.
JOURNAL OF MOLECULAR LIQUIDS
(2023)
Article
Biochemistry & Molecular Biology
Abdelbaset Mohamed Elasbali, Waleed Abu Al-Soud, Hassan H. Alhassan, Afnan Elayyan Mousa Elayyan, Mehnaz Kamal, Hamad Alanazi, Bandar Alharby, Salem Hussain Alharethi, Bashir M. Mohamed
Summary: SphK1 dysfunction is associated with various severe diseases. Small molecule inhibitors with high specificity and efficacy are needed for therapeutic use. Through a structure-based virtual screening, two compounds, Gummadiol and Isoarboreol, were identified as promising inhibitors of SphK1.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Shilpi Sarkar, Thirukumaran Kandasamy, Rajib Shome, Siddhartha Sankar Ghosh
Summary: This study highlights the involvement of epigenomic reprogramming and the role of p300 in breast cancer. By using virtual screening and molecular docking, two potential repurposed drugs, Netarsudil and Imatinib, were identified as inhibitors of p300 activity.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Chemistry, Medicinal
Lianxiang Luo, Ai Zhong, Qu Wang, Tongyu Zheng
Summary: In this study, marine natural compound 51320 was identified as a small molecule inhibitor of PD-L1 through various screening methods.
Review
Biochemistry & Molecular Biology
Helena Perez-Pena, Anne-Catherine Abel, Maxim Shevelev, Andrea E. E. Prota, Stefano Pieraccini, Dragos Horvath
Summary: Microtubules are essential in cellular processes and have potential as targets for cancer and neurodegeneration research. However, current tubulin binders have limitations, making the discovery of safer and more efficient agents necessary. Computer-aided design techniques and accessible tubulin-ligand structures can aid in the selection and design of new tubulin-targeting agents.
Article
Biochemistry & Molecular Biology
Balaji Wamanrao Matore, Partha Pratim Roy, Jagadish Singh
Summary: Currently, the development of new and effective anticancer drugs is necessary due to the limitations and drawbacks of current chemotherapeutic agents. In this study, a 3D QSAR Pharmacophore model was developed and validated using phthalimide derivatives, which showed potential anticancer activity. Through extensive analysis and simulations, it was discovered that the lead compound ASN 03206926 has strong affinity and stability as a VEGFR2-TK inhibitor. The results suggest that ASN 03206926 could be employed for the treatment of breast and VEGFR2-TK associated cancers.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Review
Chemistry, Multidisciplinary
Alejandro Varela-Rial, Maciej Majewski, Gianni De Fabritiis
Summary: Virtual screening methods, such as molecular docking and physical-based molecular simulations, offer different advantages and limitations in drug discovery. While molecular docking provides fast results using approximations, physical-based simulations offer more accurate models but require expensive computing infrastructure. Both approaches are useful for solving different aspects of the drug discovery process.
WILEY INTERDISCIPLINARY REVIEWS-COMPUTATIONAL MOLECULAR SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Boqian Zhou, Yongguang Zhang, Wanyun Jiang, Haiyang Zhang
Summary: This study used computational methods to perform virtual screening of FDA-approved drugs and identified potential inhibitors against ALDH2. Some compounds showed a low toxicity and comparable or stronger binding strength than known potent inhibitors. However, further verification is needed to confirm the efficacy of these compounds.
Article
Biochemistry & Molecular Biology
P. M. Gurubasavaraja Swamy, Nahid Abbas, Prasad Sanjay Dhiwar, Ekta Singh, Abhishek Ghara, Arka Das
Summary: In this study, a 3D QSAR pharmacophore model was generated using substituted pyrimidine class of Aurora-A kinase inhibitors, revealing the crucial role of molecular features in inhibitory activity. Five potential compounds were identified through screening and docking, demonstrating their distinctive ability to inhibit Aurora-A kinase.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Pharmacology & Pharmacy
Xinbo Yang, Xianrong Xing, Yirui Liu, Yuanjie Zheng
Summary: This study proposes a virtual drug screening method based on the M-pro structure to identify potential therapeutic drugs for COVID-19. Five compounds were found to have potential inhibitory effects on the SARS-CoV-2 M-pro, and further experimental verification was carried out.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Chemistry, Physical
Kaushikkumar A. Bhakhar, Normi D. Gajjar, Kunjan B. Bodiwala, Dipen K. Sureja, Tejas M. Dhameliya
Summary: Tuberculosis is one of the top 10 causes of communicable disease deaths worldwide, and the mmpL3 target protein plays a crucial role in synthesizing essential components of the mycobacterial outer membrane. The search for new anti-tubercular agents through computational chemistry has provided a promising start in the field of molecular modeling for mmpL3 inhibitors.
JOURNAL OF MOLECULAR STRUCTURE
(2021)
Article
Biochemistry & Molecular Biology
Changyong Deng, Xiaobo Wang, Tangle Wang, Wei Liu, Xiaolan Yuan, Yan Huang, Shuang Cao
Summary: In this study, compound 4 was identified as a promising drug candidate against the drug-resistant influenza virus strain M2-V27A/S31N. Molecular dynamics simulation showed that compound 4 had stability and flexibility when binding to the target protein. The calculated binding free energy was -106.525 kcal/mol. Physicochemical and pharmacokinetic profiles predicted good bioavailability for compound 4.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Lukasz T. Olenginski, Wojciech K. Kasprzak, Solomon K. Attionu, Bruce A. Shapiro, Theodore K. Dayie
Summary: Discovering and designing novel antiviral drugs is crucial to combat the global burden of hepatitis B virus (HBV) infection. This study focuses on epsilon, a cis-acting regulatory RNA located at the ends of the pre-genomic RNA, as a potential therapeutic target for HBV. By using the anti-hepatitis C virus drug Daclatasvir, the study demonstrates the effectiveness of targeting epsilon dynamics as an anti-HBV therapeutic strategy.
Article
Chemistry, Physical
Mahdiye Poorsargol, Abbas Rahdar, Francesco Baino, Pouya Karimi
Summary: In this study, a quercetin-loaded microemulsion was designed and the mechanism of action of quercetin in both bulk and microemulsion forms was investigated using simulation techniques. The simulation results showed that quercetin molecules quickly accumulated around 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals in the bulk form, while the accumulation was slower in the microemulsion form. The stable release of quercetin in the microemulsion form was found to be due to strong van der Waals interactions between quercetin and F127.
JOURNAL OF MOLECULAR LIQUIDS
(2023)
Article
Biochemistry & Molecular Biology
Sergio de Albuquerque, Lorenzo Cianni, Daniela de Vita, Carla Duque, Ana S. M. Gomes, Paula Gomes, Charles Laughton, Andrei Leitao, Carlos A. Montanari, Raphael Montanari, Jean F. R. Ribeiro, Joao Santana da Silva, Catia Teixeira
CHEMICAL BIOLOGY & DRUG DESIGN
(2020)
Article
Multidisciplinary Sciences
Francesco Colizzi, Modesto Orozco
Summary: The study utilizes coevolutionary information, multiscale molecular simulations, and free-energy methods to quantify allosteric regulations of protein complexes, revealing a simple ON/OFF regulation of AC by stimulatory and inhibitory G proteins. The approach provides a general strategy for exploring uncharted functional space in complex biomolecular regulations.
Article
Chemistry, Physical
Keverne A. Louison, Ian L. Dryden, Charles A. Laughton
Summary: This approach uses machine learning to transform molecular models between different levels of resolution, requiring only particle coordinates for training, and enabling bidirectional transformation.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2021)
Review
Biophysics
Gabriela da Rosa, Leandro Grille, Victoria Calzada, Katya Ahmad, Juan Pablo Arcon, Federica Battistini, Genis Bayarri, Thomas Bishop, Paolo Carloni, Thomas Cheatham Iii, Rosana Collepardo-Guevara, Jacek Czub, Jorge R. Espinosa, Rodrigo Galindo-Murillo, Sarah A. Harris, Adam Hospital, Charles Laughton, John H. Maddocks, Agnes Noy, Modesto Orozco, Marco Pasi, Alberto Perez, Daiva Petkeviciute-Gerlach, Rahul Sharma, Ran Sun, Pablo D. Dans
Summary: The structure and dynamical properties of B-DNA have long been a central topic in biology, chemistry, and physics, with its flexibility and structural polymorphism affecting its functionality and regulation. Understanding the sequence-dependent structural properties of B-DNA helps to rationalize its interactions with ligands and proteins, revealing the structural basis of gene regulation.
BIOPHYSICAL REVIEWS
(2021)
Article
Biochemical Research Methods
Genis Bayarri, Pau Andrio, Adam Hospital, Modesto Orozco, Josep Lluis Gelpi
Summary: The BioBB REST API extends and complements the BioBB library, offering programmatic access to the collection of biomolecular simulation tools included in the BioExcel Building Blocks library.
Article
Biochemistry & Molecular Biology
Genis Bayarri, Pau Andrio, Modesto Orozco, Josep Lluis Gelpi
Summary: BioExcel Building Blocks Workflows is a web-based graphical user interface that provides access to a collection of pre-configured biomolecular simulation workflows. It offers a high level of interactivity and integrates multiple tools and features to streamline common processes in biomolecular simulation.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
James P. Farmer, Shailesh N. Mistry, Charles A. Laughton, Nicholas D. Holliday
Summary: This study developed fluorescent-labeled peptides as novel binding and activation biosensors for the GPCR-IAM site, allowing the assessment of the affinity of unlabeled ligands for the receptor and providing a new method for screening IAMs. Moreover, this method can be used to investigate the efficacy of orthosteric agonists and the dynamics of receptor activation.
Article
Chemistry, Physical
Mirko Paulikat, Juan Aranda, Emiliano Ippoliti, Modesto Orozco, Paolo Carloni
Summary: The authors used classical molecular dynamics and quantum mechanics/molecular mechanics methods to investigate proton transfer processes in N-ESI/IM-MS, and validated the simulation results with experimental data. The study revealed that the distribution of protons depends on the hydration level of the analytes and the size of droplets formed during electrospray experiments.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2022)
Article
Biochemistry & Molecular Biology
Aakash Basu, Dmitriy G. Bobrovnikov, Basilio Cieza, Juan Pablo Arcon, Zan Qureshi, Modesto Orozco, Taekjip Ha
Summary: In this study, we comprehensively characterized the mechanical code of DNA using high-throughput experimental methods and developed a physical model to describe the sequence and methylation dependence of DNA deformation. Our measurements and model validations demonstrated that sequence and epigenetic modifications can encode regulatory information in diverse contexts.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Israel Serrano-Chacon, Bartomeu Mir, Lorenzo Cupellini, Francesco Colizzi, Modesto Orozco, Nuria Escaja, Carlos Gonzalez
Summary: We studied a DNA oligonucleotide that forms two different i-motif structures depending on pH and temperature. At neutral pH, the major structure is stabilized by C:C+ base pairs and G:C:G:C tetrads. At pH 5, a more elongated i-motif structure with C:C+ base pairs and G:T:G:T tetrads is observed. Molecular dynamics calculations showed that the conformational transition between the two structures is driven by the protonation state of key cytosines. This study reveals the pH-dependent plasticity and conformational switch of i-motif structures.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Medicinal
Federica Battistini, Alba Sala, Adam Hospital, Modesto Orozco
Summary: The properties of DNA duplex have been accurately described using molecular dynamics simulations, but there lacks equivalent simulations for RNA duplex which is usually represented as a rigid rod. In this study, a massive simulation effort was conducted to derive the properties of RNA duplex and a simplified model for long RNA duplexes. Despite high chemical similarity, the local and global elastic properties of DNA and RNA duplexes are significantly different. Statement about the relative flexibility or stability of both polymers is meaningless and a detailed description depending on the sequence and deformation type should be used.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Chemistry, Multidisciplinary
Israel Serrano-Chacon, Bartomeu Mir, Lorenzo Cupellini, Francesco Colizzi, Modesto Orozco, Nu'ria Escaja, Carlos Gonzalez
Summary: We studied a DNA oligonucleotide that can form two different i-motif structures, with their stability depending on pH and temperature. The structure at neutral pH is stabilized by C:C+ base pairs and G:C:G:C tetrads. At pH 5, a more elongated structure consisting of C:C+ base pairs and G:T:G:T tetrads is observed. The transition between these two structures is driven by the protonation state of key cytosines.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Biochemistry & Molecular Biology
Maysaa M. Saleh, Duaa A. Abuarqoub, Alaa M. Hammad, Md Shahadat Hossan, Najneen Ahmed, Nazneen Aslam, Abdallah Y. Naser, Christopher J. Moody, Charles A. Laughton, Tracey D. Bradshaw
Summary: In this study, the anticancer activity of the bis-triazoles MS47 and MS49 was investigated, focusing on the human melanoma MDA-MB-435 cell line. MS47 showed selective cytotoxicity against melanoma and other cancer cell lines, with sub-micromolar GI(50) and LC50 values. Both MS47 and MS49 were found to inhibit cell growth and induce apoptosis in MDA-MB-435 cells, while MS47 also arrested cells at the G0/G1 phase. Furthermore, MS49 decreased Hsp90 protein expression in melanoma cells, indicating its binding to the G4-DNA promoter of the Hsp90 gene.
CURRENT ISSUES IN MOLECULAR BIOLOGY
(2023)
Article
Chemistry, Physical
Juan Aranda, Milosz Wieczor, Montserrat Terrazas, Isabelle Brun-Heath, Modesto Orozco
Summary: We used molecular dynamics, statistical mechanics, and hybrid quantum mechanics/molecular mechanics simulations to elucidate the replication mechanism of SARS-CoV-2 RNA-dependent RNA polymerase (RdRp). Our findings showed that the viral RdRp is highly processive and has a higher catalytic rate of incorporation compared to human RNA Pol II. Furthermore, we observed that remdesivir, an antiviral nucleotide, is incorporated more slowly into the RNA than ATP, suggesting it is not a competitive inhibitor. Overall, this study provides a detailed understanding of the replication mechanism of RdRp.
Article
Chemistry, Multidisciplinary
Ioanna Danai Styliari, Vincenzo Taresco, Andrew Theophilus, Cameron Alexander, Martin Garnett, Charles Laughton