Article
Biochemical Research Methods
Qilong Wu, Sheng-You Huang
Summary: Covalent inhibitors have attracted attention for their long residence time, high binding efficiency, and strong selectivity. The development of computational tools like HCovDock, an efficient docking algorithm for covalent protein-ligand interactions, is valuable for modeling and screening of covalent drugs. HCovDock outperforms seven other state-of-the-art covalent docking programs and exhibits a high success rate in reproducing experimentally observed structures and virtual screening.
BRIEFINGS IN BIOINFORMATICS
(2023)
Article
Biochemical Research Methods
Qilong Wu, Sheng-You Huang
Summary: Covalent inhibitors are highly valued for their long residence time, high binding efficiency, and strong selectivity. The development of computational tools like molecular docking, such as HCovDock, is important for modeling covalent protein-ligand interactions and screening potential drugs. HCovDock shows better performance than other state-of-the-art docking programs and has high success rates in reproducing experimentally observed structures.
BRIEFINGS IN BIOINFORMATICS
(2022)
Article
Biochemical Research Methods
Yajun Dai, Yang Li, Liping Wang, Zhenling Peng, Jianyi Yang
Summary: In this study, the protein-ligand interactions in monomeric and quaternary structures were compared using molecular docking experiments and binding free energy estimations. The results showed that ligands in quaternary structures can simultaneously interact with multiple protein chains, and quaternary structures have lower binding free energy and more accurate ligand conformations compared to monomeric structures. Therefore, it is recommended to use quaternary structures in future studies on protein-ligand interactions.
IEEE-ACM TRANSACTIONS ON COMPUTATIONAL BIOLOGY AND BIOINFORMATICS
(2022)
Review
Physics, Applied
Connor J. Morris, Dennis Della Corte
Summary: Molecular docking and molecular dynamics are powerful tools for studying protein-ligand interactions, predicting binding poses, affinities, and stability. They are widely used in drug discovery and further research on combining common molecular docking and MD methods is recommended for enhanced results.
MODERN PHYSICS LETTERS B
(2021)
Article
Biochemistry & Molecular Biology
Hugo Guterres, Sang-Jun Park, Han Zhang, Thomas Perone, Jongtaek Kim, Wonpil Im
Summary: Molecular docking is a popular computational tool in drug design, but has room for improvement. Molecular dynamics (MD) simulations of protein-ligand structures can enhance docking accuracy, and the CHARMM-GUI high-throughput simulator (HTS) is a tool for preparing MD simulation systems.
Article
Chemistry, Multidisciplinary
Simin Nazari, Amira Abdelrasoul
Summary: This study explores the impact of surface modification with zwitterionic materials on the hemocompatibility of hemodialysis membranes. The results show that membranes with zwitterions of opposite dipole orientations have better protein-ligand interactions and antifouling properties, leading to higher hemocompatibility and efficiency in hemodialysis.
APPLIED SCIENCES-BASEL
(2023)
Review
Pharmacology & Pharmacy
Yuyu Feng, Yumeng Yan, Jiahua He, Huanyu Tao, Qilong Wu, Sheng-You Huang
Summary: Nucleic acid-ligand interactions play crucial roles in cellular processes and have attracted significant interest in drug discovery. However, traditional docking algorithms and scoring functions for protein-ligand interactions may not be applicable to nucleic acid-ligand docking due to the differences in their properties. This review discusses the current status, challenges, and limitations of docking algorithms and scoring functions for DNA/RNA-ligand interactions.
DRUG DISCOVERY TODAY
(2022)
Article
Biochemical Research Methods
Xiaocong Yang, Yang Liu, Jianhong Gan, Zhi-Xiong Xiao, Yang Cao
Summary: Protein-ligand docking is crucial in drug design and bioinformatics. FitDock, a new method, has shown significant improvement in docking success rate and speed compared to popular methods, especially when template structures are available.
BRIEFINGS IN BIOINFORMATICS
(2022)
Article
Biochemistry & Molecular Biology
Bei Zhang, Yue Huang, Si-Rui Zhang, Meng-Xing Huang, Chen Zhang, Hai-Bin Luo
Summary: Phosphodiesterase-1 (PDE1) is a promising drug target for central and peripheral diseases. Through molecular docking and dynamics simulations, a series of pyrazolopyrimidone derivatives were designed as effective PDE1 inhibitors, with most compounds showing good inhibitory activities and compound 2j demonstrating good metabolic stability. This compound can be utilized as a tool to explore the molecular recognition mechanism between inhibitors and the target protein PDE1.
BIOORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Tanumoy Banerjee, Agnivo Gosai, Niloofar Yousefi, Ozlem Ozmen Garibay, Sudipta Seal, Ganesh Balasubramanian
Summary: Severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) is the primary cause of the global COVID-19 pandemic that has affected millions of lives worldwide. The infection occurs when the viral spike protein receptor binding domain (SP-RBD) binds to the human cell angiotensin-converting enzyme 2 (ACE2) receptor. Sialic acid-based molecules show strong binding affinity to SP RBD and have the potential to serve as inhibitors to prevent the binding of RBD-ACE2.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Gianvito Grasso, Arianna Di Gregorio, Bojan Mavkov, Dario Piga, Giuseppe Falvo D'Urso Labate, Andrea Danani, Marco A. Deriu
Summary: In this paper, a novel blind docking protocol based on Autodock-Vina is proposed, which combines binding site identification and binding pose prediction through systematic exploration of protein volume. With the application of MM/GBSA re-scoring procedures, the accuracy of protein-ligand bound state can be improved. Tested on various protein-ligand complexes, the FRAD approach combined with MM/GBSA re-scoring is considered a powerful tool to increase accuracy and efficiency, especially when the ligand-binding site is unknown.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Computer Science, Artificial Intelligence
Shuangbao Song, Xingqian Chen, Yanxin Zhang, Zheng Tang, Yuki Todo
Summary: This study utilizes an adaptive differential evolution algorithm and the scoring function of AutoDock Vina to address the protein-ligand docking problem, with experimental results indicating its effectiveness compared to other evolutionary algorithms.
KNOWLEDGE-BASED SYSTEMS
(2021)
Article
Chemistry, Physical
Ramon Rial, Michael Gonzalez-Durruthy, Zhen Liu, Juan M. Ruso
Summary: This study provides an in-depth analysis of the binding process between two antibiotics and a blood serum protein, revealing that both penicillins are moderate binders with hydrogen bond and van der Waals forces being predominant. The study emphasizes the importance of approaching these systems from both atomic and macromolecular perspectives.
JOURNAL OF MOLECULAR LIQUIDS
(2022)
Article
Chemistry, Medicinal
Kushagra Kashyap, Pinaki Prasad Mahapatra, Shakil Ahmed, Erdem Buyukbingol, Mohammad Imran Siddiqi
Summary: In this study, a 3D convolutional neural network-based ALR2 inhibitor classification technique was developed, which successfully identified the top 10 compounds with high binding affinity. These compounds exhibited superior blood-brain barrier penetration efficiency and potential ALR2 inhibition activity, making them promising candidates for further research and optimization as anti-diabetic neuropathy drugs.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Biology
Mohd Afzal, Abdullah Alarifi, Naaser. A. Y. Abduh, Arusha Ayub, Mohd. Muddassir
Summary: Apoptosis is regulated by the BCL-2 family, and inhibition of the pro-apoptotic and anti-apoptotic protein-protein interactions has been studied for developing anticancer drugs. In this study, the hydrophobic nature of 74 organometallic compounds was analyzed, and their effectiveness against the BCL-2 protein was determined using molecular docking. The results identified several important compounds that could bind to the less solvent-accessible site of BCL-2.
COMPUTERS IN BIOLOGY AND MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Pankaj Pandey, Kuldeep K. Roy, Robert J. Doerksen
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2020)
Article
Biochemistry & Molecular Biology
Francisco F. Bezerra, William P. Vignovich, AyoOluwa O. Aderibigbe, Hao Liu, Joshua S. Sharp, Robert J. Doerksen, Vitor H. Pomin
JOURNAL OF STRUCTURAL BIOLOGY
(2020)
Article
Chemistry, Organic
Anantha Lakshmi Duddupudi, Pankaj Pandey, Hien Vo, Colin L. Welsh, Robert J. Doerksen, Gregory D. Cuny
JOURNAL OF ORGANIC CHEMISTRY
(2020)
Article
Chemistry, Medicinal
Pankaj Pandey, Bharathi Avula, Ikhlas A. Khan, Shabana Khan, Victor J. Navarro, Robert J. Doerksen, Amar G. Chittiboyina
CHEMICAL RESEARCH IN TOXICOLOGY
(2020)
Article
Biochemistry & Molecular Biology
AyoOluwa O. Aderibigbe, Pankaj Pandey, Robert J. Doerksen
Summary: The study compared computational predictions with experimental results of the ternary CB1 complex structure and the binding mode of the negative allosteric modulator at different sites on the receptor.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Biochemistry & Molecular Biology
Narayan D. Chaurasiya, Jacob Midiwo, Pankaj Pandey, Regina N. Bwire, Robert J. Doerksen, Ilias Muhammad, Babu L. Tekwani
Article
Biology
Niloofar Abolhasani Khaje, Alexander Eletsky, Sarah E. Biehn, Charles K. Mobley, Monique J. Rogals, Yoonkyoo Kim, Sushil K. Mishra, Robert J. Doerksen, Steffen Lindert, James Prestegard, Joshua S. Sharp
Summary: This study presents a mass spectrometry-based method that guides computational modeling for de novo protein structure prediction. The method was successfully used to determine the structure of a protein with no close homolog of known structure.
COMMUNICATIONS BIOLOGY
(2022)
Article
Biology
Masamichi Nagae, Tetsuya Hirata, Hiroaki Tateno, Sushil K. Mishra, Noriyoshi Manabe, Naoko Osada, Yuko Tokoro, Yoshiki Yamaguchi, Robert J. Doerksen, Toshiyuki Shimizu, Yasuhiko Kizuka
Summary: X-ray crystallography, NMR, and computer modeling were used to investigate the structure and catalytic mechanism of GnTIVa, an enzyme involved in the synthesis of GlcNAc branches. The enzyme contains a C-terminal lectin domain that regulates its activity. The lectin domain was found to interact selectively with N-glycans having a beta 1-4 GlcNAc branch. Our findings provide insights into the biosynthesis of branching structures in N-glycans.
COMMUNICATIONS BIOLOGY
(2022)
Article
Chemistry, Medicinal
Reem A. Alkhodier, Sushil K. Mishra, Robert J. Doerksen, David A. Colby
Summary: Glycosylated natural products display biological activity but are deglycosylated by metabolic processes. CF2-derivatives of natural products are challenging to synthesize. Difluorinated molecules have unique conformational behavior due to changes in the glycosidic linkage. The site of glycosylation and substitution pattern on the flavonoid determine the conformational properties. Docking study showed potential for flavonoid-CF2-glycosides to retain a similar binding pose as the parent O-glycoside.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Biochemistry & Molecular Biology
Pankaj Pandey, Mallika Kumarihamy, Krishna Chaturvedi, Mohamed A. M. Ibrahim, Janet A. Lambert, Murrell Godfrey, Robert J. Doerksen, Ilias Muhammad
Summary: Magnolia grandiflora L. is a plant with significant medicinal importance, especially its flowers and seeds. The extract of n-hexane seeds showed binding affinity to both CB1 and CB2 cannabinoid receptors. Compounds 1-3, including 4-O-methylhonokiol, had higher binding affinity to cannabinoid receptors compared to opioid receptors. Molecular docking studies revealed the importance of hydroxyl groups in the neolignan molecules for binding to CB1R and CB2R receptors.
Article
Pharmacology & Pharmacy
Anitha Police, Vijay Kumar Shankar, Pankaj Pandey, Srinath Rangappa, Robert J. Doerksen, S. Narasimha Murthy
Summary: Peripheral neuropathy (PN) is a condition characterized by peripheral nerve damage leading to severe pain. The current treatments for PN have either psychotropic side effects or are not effective enough. This study aims to find a safe inhibitor of the fatty acid amide hydrolase enzyme (FAAH) and develop a topical gel formulation to deliver anandamide, an endocannabinoid that relieves PN pain. The results showed that silymarin constituents, particularly silybin, demonstrated significant FAAH inhibition potential and increased the half-life of anandamide. The developed gel formulation increased the permeation of anandamide and silybin, resulting in a significant increase in pain threshold in rat models of PN.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2023)
Article
Biology
Priyanka Samanta, Robert J. Doerksen
Summary: Nearly 50% of women experience urinary tract infections (UTIs) in their lifetimes, and the main culprit is Uropathogenic Escherichia coli (UPEC). UPEC uses a specific type of pilus called F9/Yde/Fml, which binds to glycoproteins in the cells of the bladder and kidney. However, the overuse of antibiotics has led to the emergence of antibiotic-resistant UPEC strains. In this study, computational modeling techniques were used to design small molecules that can bind to FmlH, a key component of the pilus. The screening protocol developed here could be applied to other similar protein targets, and a database of potential FmlH inhibitors was also provided.
COMPUTERS IN BIOLOGY AND MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Priyanka Samanta, Sushil K. Mishra, Vitor H. Pomin, Robert J. Doerksen
Summary: This study conducted a computational analysis on the binding of four oligosaccharide building blocks from novel marine sulfated glycans to the receptor-binding domain of SARS-CoV-2. It identified two binding sites and revealed the key structural features and interactions driving ligand binding. This study provided important structural information for the development of these novel glycans as potential therapeutics.
Article
Chemistry, Medicinal
Tomayo Berida, Samuel R. Mckee, Shamba Chatterjee, Destinee L. Manning, Wei Li, Pankaj Pandey, Siddharth Kaushal Tripathi, Yassin Mreyoud, Asya Smirnov, Robert J. Doerksen, Mary Jackson, Christian Ducho, Christina L. Stallings, Sudeshna Roy
Summary: The increase in multidrug-resistant cases of tuberculosis highlights the urgency of developing new treatment strategies. In this study, a series of compounds containing a 3-thio-1,2,4-triazole moiety were discovered and synthesized. These compounds exhibited inhibitory activity against Mycobacterium tuberculosis (Mtb) growth and survival. Structure-activity relationship studies identified several potent analogs with low micromolar to nanomolar inhibitory activity against Mtb. These potent analogs showed no cytotoxicity in mammalian cells and were bactericidal against Mtb during infection of macrophages. Further investigations into the mechanism of action revealed potential metabolic liabilities for optimization. The findings suggest the potential of these compounds as a new class of 1,2,4-triazole compounds for tuberculosis treatment.
ACS INFECTIOUS DISEASES
(2023)
Article
Environmental Sciences
Kamel Mansouri, Agnes L. Karmaus, Jeremy Fitzpatrick, Grace Patlewicz, Prachi Pradeep, Domenico Alberga, Nathalie Alepee, Timothy E. H. Allen, Dave Allen, Vinicius M. Alves, Carolina H. Andrade, Tyler R. Auernhammer, Davide Ballabio, Shannon Bell, Emilio Benfenati, Sudin Bhattacharya, Joyce Bastos, Stephen Boyd, J. B. Brown, Stephen J. Capuzzi, Yaroslav Chushak, Heather Ciallella, Alex M. Clark, Viviana Consonni, Pankaj R. Daga, Sean Ekins, Sherif Farag, Maxim Fedorov, Denis Fourches, Domenico Gadaleta, Feng Gao, Jeffery M. Gearhart, Garett Goh, Jonathan M. Goodman, Francesca Grisoni, Christopher M. Grulke, Thomas Hartung, Matthew Hirn, Pavel Karpov, Alexandru Korotcov, Giovanna J. Lavado, Michael Lawless, Xinhao Li, Thomas Luechtefeld, Filippo Lunghini, Giuseppe F. Mangiatordi, Gilles Marcou, Dan Marsh, Todd Martin, Andrea Mauri, Eugene N. Muratov, Glenn J. Myatt, Dac-Trung Nguyen, Orazio Nicolotti, Reine Note, Paritosh Pande, Amanda K. Parks, Tyler Peryea, Ahsan H. Polash, Robert Rallo, Alessandra Roncaglioni, Craig Rowlands, Patricia Ruiz, Daniel P. Russo, Ahmed Sayed, Risa Sayre, Timothy Sheils, Charles Siegel, Arthur C. Silva, Anton Simeonov, Sergey Sosnin, Noel Southall, Judy Strickland, Yun Tang, Brian Teppen, Igor Tetko, Dennis Thomas, Valery Tkachenko, Roberto Todeschini, Cosimo Toma, Ignacio Tripodi, Daniela Trisciuzzi, Alexander Tropsha, Alexandre Varnek, Kristijan Vukovic, Zhongyu Wang, Liguo Wang, Katrina M. Waters, Andrew J. Wedlake, Sanjeeva J. Wijeyesakere, Dan Wilson, Zijun Xiao, Hongbin Yang, Gergely Zahoranszky-Kohalmi, Alexey Zakharov, Fagen F. Zhang, Zhen Zhang, Tongan Zhao, Hao Zhu, Kimberley M. Zorn, Warren Casey, Nicole C. Kleinstreuer
Summary: The international collaboration in developing in silico models for predicting acute oral toxicity, resulting in the CATMoS, has demonstrated high performance in terms of accuracy and robustness. This modeling suite is being evaluated by regulatory agencies as a potential replacement for in vivo rat acute oral toxicity studies.
ENVIRONMENTAL HEALTH PERSPECTIVES
(2021)
Article
Chemistry, Multidisciplinary
Michal Novotny, Matus Dubecky, Frantisek Karlicky
Summary: This paper investigates the accuracy of different DFT-based computational approaches in calculating the equilibrium lattice constants and exfoliation energy of hexagonal boron nitride (h-BN). The results are compared with experiments and reference QMC calculations to evaluate the accuracy of these computational methods.
JOURNAL OF COMPUTATIONAL CHEMISTRY
(2024)
Article
Chemistry, Multidisciplinary
Luigi Crisci, Federico Coppola, Alessio Petrone, Nadia Rega
Summary: The charge transfer dynamics in asymmetrically substituted indenotetracene molecules upon photo-excitation were investigated using real-time time-dependent density functional theory simulations. The study found that the electron-donating character of the substituents affects the overall electronic energy spacing and ultrafast charge transfer dynamics.
JOURNAL OF COMPUTATIONAL CHEMISTRY
(2024)
Article
Chemistry, Multidisciplinary
Vasilii Korotenko, Hendrik Zipse
Summary: The stability of various radicals and molecules has been studied using different theoretical methods, and good correlations between theoretical calculations and experimental results have been found. The effects of hydrogen bonding interactions on the stability of oxygen-centered radicals have also been investigated.
JOURNAL OF COMPUTATIONAL CHEMISTRY
(2024)
Article
Chemistry, Multidisciplinary
Oleg Egorov, Michael Rey, Dominika Viglaska, Andrei V. Nikitin
Summary: In this work, the rovibrational energy levels of four isotopologues of methylene were calculated using a new accurate ab initio potential energy surface. The accuracy of the calculations was improved by considering scalar relativistic effects, DBOC, and high-order electronic correlations. For the first time, all available experimental rovibrational transitions were reproduced with high accuracy, without any empirical corrections.
JOURNAL OF COMPUTATIONAL CHEMISTRY
(2024)