Article
Pharmacology & Pharmacy
Shiyu Wang, Xiaolin Sun, Wenqiang Cui, Shuguang Yuan
Summary: This study presents a rapid and accurate method, MM/PB(GB)SA, for predicting protein-ligand binding free energy. Benchmark tests conducted on multiple systems show that MM/PB(GB)SA performs competitively with other methods such as docking and free energy perturbation. The optimization of parameters, such as GB models and membrane dielectric constants, is necessary for different systems. MM/PB(GB)SA can serve as a powerful tool for drug design.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Spectroscopy
S. Arsenault-Escobar, J. F. Fuentes-Galvez, C. Orellana, S. Bollo, P. Sierra-Rosales, S. Miranda-Rojas
Summary: In this study, we investigated the interaction between the food colorant tartrazine (TZ) and double stranded DNA (dsDNA) using spectroscopic, electrochemical, and computational methods. By combining UV-vis experiments with high-level computational models, we were able to determine the proper binding mode at the molecular scale and explain the experimental optical response due to the complex formation. In addition, we used electrochemical measurements to support the results obtained through UV-vis spectroscopy. Our findings showed that TZ is deeply buried in the DNA, as evidenced by the hypochromic effect observed in the absorption spectra.
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
(2023)
Article
Biochemical Research Methods
Zhe Wang, Hong Pan, Huiyong Sun, Yu Kang, Huanxiang Liu, Dongsheng Cao, Tingjun Hou
Summary: The fastDRH server is a free and open accessed web platform for predicting and analyzing protein-ligand complex structures. It integrates multiple features such as molecular docking, docking pose rescoring, and hotspot residue prediction to provide key information to users clearly. With a success rate of >80% in benchmark for protein-ligand binding mode prediction, the fastDRH server is a reliable tool for drug discovery projects.
BRIEFINGS IN BIOINFORMATICS
(2022)
Article
Biochemistry & Molecular Biology
Yang Cong, Yu Zhai, Xin Chen, Hui Li
Summary: This study validates the performance of several semi-empirical quantum chemistry methods in describing soot formation and discusses their limitations and applicability. The results show that these methods are qualitatively accurate but cannot provide quantitatively accurate data.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Mathematics, Applied
Yangshuai Wang, Huajie Chen, Mingjie Liao, Christoph Ortner, Hao Wang, Lei Zhang
Summary: Hybrid quantum/molecular mechanics models, known as QM/MM methods, are commonly used in material and molecular simulations to strike a balance between accuracy and computational cost. Adaptive QM/MM coupling methods, with on-the-fly classification of atoms, allow for real-time updates of the QM and MM subsystems as needed. This study proposes a new adaptive QM/MM method for material defect simulations based on a residual from a posteriori error estimator, showcasing its effectiveness through numerical simulations.
SIAM JOURNAL ON SCIENTIFIC COMPUTING
(2021)
Article
Mathematics, Interdisciplinary Applications
Huajie Chen, Christoph Ortner, Yangshuai Wang
Summary: This paper presents a framework for consistent QM/MM hybrid models of crystalline defects, allowing for general atomistic interactions including traditional and machine-learned interatomic potentials. The authors establish an a priori error estimate for the QM/MM approximations and demonstrate how matching conditions can be used to construct practical machine learned MM potentials for QM/MM simulations.
MULTISCALE MODELING & SIMULATION
(2022)
Article
Chemistry, Multidisciplinary
Rakesh Kumar Tiwari, Vinayak Pandey, Harshita Srivastava, Ambrish Kumar Srivastava, Vishnudatt Pandey
Summary: The hydrophobic residues Gly 81, Phe 133, and Ile 147 in the interface between the MTase domain and RdRp of NS5 protein may play a key role in stabilizing the crucial residues involved in enzymatic activity.
FRONTIERS IN CHEMISTRY
(2023)
Article
Chemistry, Analytical
Frederik G. Tidemand, Andrea Zunino, Nicolai T. Johansen, Anna Freja Hansen, Peter Westh, Klaus Mosegaard, Lise Arleth
Summary: ANISPROU is a software that extracts quantitative information from complex ITC data through a semi-empirical method, addressing the issue of ITC data analysis in multifaceted cases and providing a more automated and objective analysis compared to existing methods.
ANALYTICAL CHEMISTRY
(2021)
Article
Chemistry, Physical
Risnita Vicky Listyarini, Bernhard M. Kriesche, Thomas S. Hofer
Summary: In this work, the structural and dynamical properties of CO2 in dichloromethane were studied using various computational methods. The results show that all levels of theory provide a similar description of the first solvation layer. The RI B3LYP-D3 method agrees well with the high-level RI MP2 reference, while the SCC DFTB/3ob and GFN2-xTB methods have minor deficiencies in describing halogen-based interactions. The vibrational frequencies of the solute and the residence times of the first shell ligands show similar values, indicating rapid exchange reactions with the bulk. Additionally, classical potential models were assessed and adjusted to provide comparable structural and dynamical data to the more expensive quantum chemical methods.
JOURNAL OF MOLECULAR LIQUIDS
(2022)
Article
Biochemical Research Methods
Maohua Yang, Zonghua Bo, Tao Xu, Bo Xu, Dongdong Wang, Hang Zheng
Summary: This article introduces a user-friendly automatic workflow, Uni-GBSA, for performing MM/GB(PB)SA calculations, which is very useful for binding free energy calculations of ligands to protein receptors in drug discovery.
BRIEFINGS IN BIOINFORMATICS
(2023)
Article
Biochemical Research Methods
Carlos A. Ortiz-Mahecha, William A. Agudelo, Manuel A. Patarroyo, Manuel E. Patarroyo, Carlos F. Suarez
Summary: Estimating peptide-major histocompatibility complex (pMHC) binding affinity experimentally is challenging due to the involvement of many receptors and potential ligands. A computational methodology considering different mechanisms has been proposed to facilitate studying receptor-ligand interactions. A pipeline using semi-empirical quantum mechanical methods has been developed to calculate pMHC class I and II molecules' binding energy (BE), enabling rational design of T-cell epitopes for pharmaceutical and vaccine purposes.
BRIEFINGS IN BIOINFORMATICS
(2021)
Review
Chemistry, Multidisciplinary
Himani Sharma, Baddipadige Raju, Gera Narendra, Mohit Motiwale, Bhavna Sharma, Himanshu Verma, Om Silakari
Summary: Computational enzymology is a rapidly developing field that provides deep insights into the process of biological catalysis, aiding in the design of potential inhibitors. The combined quantum mechanics/molecular mechanics approach has gained attention for understanding enzymatic reactions at both structural and energetic levels. It offers a new mechanism for designing potent enzyme inhibitors.
Article
Biochemistry & Molecular Biology
Sijin Chen, Xiaoyan Ding, Chao Sun, Anthony Watts, Xiao He, Xin Zhao
Summary: The study investigated the dynamic coupling of Y185 with the bR photocycle through calculations and simulations, revealing its significant role in regulating thermal equilibrium, stabilizing H-bond networks, participating in orientation switch, and opening the channel gate. These findings provide a detailed molecular mechanism of the dynamic couplings of Y185 and the bR photocycle from a structural perspective, with potential applications to other microbial photoreceptors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Phillip S. Hudson, Felix Aviat, Ruben Meana-Paneda, Luke Warrensford, Benjamin C. Pollard, Samarjeet Prasad, Michael R. Jones, H. Lee Woodcock, Bernard R. Brooks
Summary: Accurately predicting free energy differences is crucial for rational drug design. This study focuses on the computation of QM/MM binding free energies and evaluates different QM/MM correction methods in the context of the SAMPL8 Drugs of Abuse host-guest challenge.
JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN
(2022)
Review
Physics, Multidisciplinary
O. Lopez-Acevedo, D. Sucerquia
Summary: In this article, the applications of the QM/MM method in the study of interactions between copper, silver, and gold atoms/clusters and biological/organic molecules are reviewed. Various research efforts are highlighted, demonstrating the successful application of the QM/MM method in studying excited state evolution, charge transport, light absorption and emission, and determining atomic structures.
ADVANCES IN PHYSICS-X
(2023)
Article
Biochemistry & Molecular Biology
Sreevidya S. Devi, Vandana Kardam, Kshatresh D. Dubey, Manish Dwivedi
Summary: In this study, the reverse vaccinology approach was used to identify T-cell epitopes suitable for the Indian population, providing important clues for designing a vaccine against SARS-CoV-2.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Chemistry, Medicinal
Shalini Yadav, Sason Shaik, Shakir Ali Siddiqui, Surajit Kalita, Kshatresh Dutta Dubey
Summary: This study investigates the P450(OleT) and P450(Bs beta) enzymes using QM/MM calculations and MD simulations. The study reveals that the protonated His85 in P450(OleT) plays a crucial role in stabilizing the corresponding hydroxoiron(IV) intermediate, leading to decarboxylation. In contrast, P450(Bs beta) with Q85 instead of H85 produces hydroxylation products through rebound. The single-site difference creates a different local electric field (LEF) in P450(OleT), which accounts for the different stabilities and functions of the two enzymes.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Medicine, Research & Experimental
Anil Kumar, Jyoti Chauhan, Kshatresh Dutta Dubey, Subhabrata Sen, Parthapratim Munshi
Summary: Polymorphism plays a critical role in drug development, and can enhance the biological potency of bioactive molecules. This study focuses on the analysis of multiple polymorphs and their impact on the inhibition of cancer cell proliferation.
MOLECULAR PHARMACEUTICS
(2022)
Article
Chemistry, Physical
Shakir Ali Siddiqui, Kshatresh Dutta Dubey
Summary: The study introduces the local electric field (LEF) of enzymes along the reaction axis as a descriptor for enzymatic activity, showing a direct correlation between the calculated enzymatic electric field (EF) and enzymatic activity for all complexes. MD simulations and calculations demonstrate the stabilizing effect of the electric field on the transition state analog (TSA), lowering the activation energy by interacting with the dipole moment of the TS.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2022)
Article
Chemistry, Physical
Surajit Kalita, Sason Shaik, Kshatresh Dutta Dubey
Summary: This study investigates the catalytic mechanism of cytochrome P450(51) in the biosynthesis of sterol. It reveals that the C-C bond cleavage reaction can initiate from either gem-diol or aldehyde intermediates, and proceeds through proton-coupled electron transfer or with assistance from a water molecule. The findings provide insights into the enigmatic reaction of C-C bond cleavage and its role in the natural biosynthesis of complex organic molecules.
Article
Chemistry, Multidisciplinary
Souvik Guha, Ibrahim Yussif El-Deeb, Shalini Yadav, Ranajit Das, Kshatresh Dutta Dubey, Mousumi Baruah, Gremaud Ludovic, Subhabrata Sen
Summary: In this study, a compound consisting of a pentacyclic building block from perophoramidine was discovered as a potent anticancer agent. The compound showed cytotoxicity against various cancer cell lines and induced DNA damage and PARP inhibition. The binding efficiency of the compound with PARP 1 enzyme was determined through molecular docking and simulation studies.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Chemistry, Multidisciplinary
Ankita Tripathi, Kshatresh Dutta Dubey
Summary: This study demonstrates a method to enhance promiscuity, called allostery-driven promiscuity, using molecular dynamics simulations and hybrid QM/MM calculations. By studying the AEE enzyme, the authors show that a single site mutation can induce conformational changes in the capping loop, allowing recognition of different substrates for different functions.
CHEMISTRY-AN ASIAN JOURNAL
(2022)
Article
Chemistry, Multidisciplinary
Surajit Kalita, Hagai Bergman, Kshatresh Dutta Dubey, Sason Shaik
Summary: Alzheimer's disease and other neurodegenerative diseases characterized by senile plaques are caused by the accumulation of s-amyloid peptides. This study investigates the behavior of these plaques in the presence of static and oscillating oriented external electric fields using molecular dynamics simulations. The results show that long-term disintegration of the plaques is desirable for therapeutic treatments. Furthermore, the use of oscillating oriented external electric fields leads to irreversible disintegration of the aggregated s-amyloid peptides.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Biochemistry & Molecular Biology
Warispreet Singh, Sonia F. G. Santos, Shalini Yadav, Gary W. Black, Kshatresh Dutta Dubey
Summary: A newly discovered heme-dependent enzyme TyrH offers a green method for functionalizing C-H and C-F bonds in aromatic compounds. Through molecular dynamics simulations and calculations, it was found that compound I acts as the primary oxidant for both C-H and C-F activation. This study reveals the importance of active site conformation in determining selective functionalization.
Article
Chemistry, Multidisciplinary
Rashmi Yadav, Subrata Munan, Vandana Kardam, Kshatresh Dutta Dubey, Animesh Samanta
Summary: Esterase enzymes play a crucial role in regulating the body's homeostasis and are involved in various important cellular processes. Developing efficient chemical probes to monitor esterase activity is essential. In this study, a unique fluorescent probe, PM-OAc, was developed to ratiometrically monitor mitochondrial esterase activity. The probe exhibited a wavelength shift with esterase enzyme in alkaline pH due to an intramolecular charge transfer process. Molecular dynamics simulation and QM/MM calculations were used to elucidate the substrate binding and catalytic mechanism of esterase. The probe showed potential for distinguishing live and dead cells based on esterase enzyme activity.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Medicinal
Jyoti Chauhan, Erika Cecon, Nedjma Labani, Florence Gbahou, Fernando Real, Morgane Bomsel, Kshatresh Dutta Dubey, Ranajit Das, Julie Dam, Ralf Jockers, Subhabrata Sen
Summary: COVID-19 is a complex disease caused by SARS-CoV-2 infection, leading to respiratory, inflammatory, and neurological symptoms. In this study, a multi-target strategy was explored by synthesizing a compound library based on C2-substituted indolealkylamines. Two compounds, 5e and h, showed high affinity for melatonin receptors and inhibited the activity of calmodulin kinase II and the interaction between SARS-CoV-2 Spike protein and hACE2. These compounds also blocked SARS-CoV-2 entry into host cells and reduced virus replication and MPro enzyme activity. This study provides a proof-of-concept for the design of multi-target compounds to treat COVID-19 and other coronavirus diseases.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Physical
Shalini Yadav, Sason Shaik, Kshatresh Dutta Dubey
Summary: CYP450(OleT) is a member of the CYP450 peroxygenases family and has unusual decarboxylation activity. However, a mutation in the 85th position from histidine to glutamine still maintains efficient decarboxylation activity. Molecular dynamics simulation reveals that an aspartic acid residue takes on a similar role via a well-organized water channel in the H85Q mutant of CYP450(OleT). This water channel is vital for substrate positioning and is regulated by the residue pair Q85-N242.
JOURNAL OF PHYSICAL CHEMISTRY B
(2023)
Article
Biology
Vikas Maurya, Raja Singh, Reman Kumar Singh, Stuti Pandey, Pooja Yadav, Palak Parashar, Rajni Gaind, Kshatresh Dutta Dubey, G. Naresh Patwari, Vibha Tandon
Summary: Type IA topoisomerases maintain DNA topology by cleaving ssDNA and relaxing negative supercoils. Inhibition of bacterial TopoIA activity by PPEF and BPVF inhibits DNA metabolic processes and leads to cell death. PPEF specifically stabilizes the topoisomerase and its complex with ssDNA, acting as an interfacial inhibitor.
COMMUNICATIONS BIOLOGY
(2023)
Article
Chemistry, Organic
Ankita Tripathi, Kshatresh Dutta Dubey
Summary: l-Homoserine kinase plays a crucial role in the biosynthesis of l-threonine, l-isoleucine, and l-methionine. A mutation of H138 -> L in this enzyme leads to the emergence of ATPase activity as a secondary function. Using computational tools, we provide new insights into the catalytic mechanism of l-homoserine kinase, showing the involvement of H138 as a catalytic base and a new water channel connecting ATP. This study has implications for enzyme engineering to synthesize amino acid analogs.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Article
Chemistry, Physical
Shalini Yadav, Sason Shaik, Kshatresh Dutta Dubey
Summary: CYP450OleT, a member of the CYP450 peroxygenases family, exhibits unique decarboxylation activity. The presence of histidine at position 85 was believed to be responsible for this activity, but mutation to glutamine still maintained efficient decarboxylation. Molecular dynamics simulations revealed that in the absence of histidine, aspartate 239 played a similar role through a well-organized water channel. This channel, regulated by the residue pair of glutamine 85 and asparagine 242, is critical for optimal substrate positioning and decarboxylation activity.
JOURNAL OF PHYSICAL CHEMISTRY B
(2023)