Article
Chemistry, Medicinal
Bharath Raghavan, Florian K. Schackert, Andrea Levy, Sophia K. Johnson, Emiliano Ippoliti, Davide Mandelli, Jogvan Magnus Haugaard Olsen, Ursula Rothlisberger, Paolo Carloni
Summary: MiMiC is a flexible and scalable multiscale modeling framework that combines quantum mechanics (QM) and molecular mechanics (MM) codes. The paragraph introduces MiMiCPy, a user-friendly tool written in Python 3 that automates the preparation of MiMiC input files. It also highlights the modular structure of MiMiCPy, allowing for easy extensions to new program formats.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Multidisciplinary Sciences
Yusuke Kanematsu, Akihiro Narita, Toshiro Oda, Ryotaro Koike, Motonori Ota, Yu Takano, Kei Moritsugu, Ikuko Fujiwara, Kotaro Tanaka, Hideyuki Komatsu, Takayuki Nagae, Nobuhisa Watanabe, Mitsusada Iwasa, Yuichiro Maeda, Shuichi Takeda
Summary: This study reveals the reaction mechanism of ATP hydrolysis by actin. Through structural analysis and calculations, the researchers have identified a specific reaction path, explaining the slow rate and irreversibility of actin ATP hydrolysis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Rabindra Nath Manna, Jose N. Onuchic, Biman Jana
Summary: Kinesin motor proteins play important roles in cellular functions by utilizing ATP hydrolysis. Mutations in the kinesin motor protein KIF5A have been linked to HSP disease. This study investigates the molecular mechanism of a specific distal mutation that affects the ATP hydrolysis reaction in kinesin. The findings provide insights into how different genetic effects on kinesin dynamics can lead to the same disease phenotype.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Shunya Suenaga, Yu Takano, Toru Saito
Summary: A quantum mechanics/molecular mechanics molecular dynamics (QM/MM MD) study was conducted on three representative competitive inhibitors of urease. The study found that N-(n-butyl)phosphorictriamide (NBPTO) exhibited the highest inhibitory activity and the lowest IC50 value, followed by acetohydroxamic acid (AHA) and hydroxyurea (HU). The structural and thermodynamical properties of the inhibitors were found to be correlated with their inhibition efficiency.
Article
Chemistry, Physical
Qiang Cui, Tanmoy Pal, Luke Xie
Summary: This article discusses the challenges and issues in QM/MM simulations, emphasizing the importance of these issues for applications in biomolecular systems. Despite its limited scope, the hope is to stimulate further developments in the field of QM/MM simulation methods.
JOURNAL OF PHYSICAL CHEMISTRY B
(2021)
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
Biochemistry & Molecular Biology
Francisco Andres Peralta, J. Pablo Huidobro-Toro, Raul Mera-Adasme
Summary: QM/MM molecular dynamic simulations were used to study the allosteric modulator role of Zn(II) on P2X4R, revealing insights into the nature of Zn(II) modulation and the effects of mutations, potentially explaining elusive modulation mechanisms in other extracellular or membrane proteins.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Phujinn Honorio, Supawadee Sainimnuan, Supa Hannongbua, Patchreenart Saparpakorn
Summary: The research discovered that protoberberine alkaloids isolated from natural resources are potent inhibitors of acetylcholinesterase (AChE) and have the potential to reduce symptoms of Alzheimer's disease. The key interactions of palmatine and berberine with AChE were identified as 7C-7C interactions with specific amino acids and H-bond interactions. In contrast, cyclanoline showed a different binding mode and preference for a deeper site within AChE.
CHEMICO-BIOLOGICAL INTERACTIONS
(2021)
Article
Chemistry, Medicinal
Sergio Boneta, Kernel Arafet, Vicent Moliner
Summary: This study investigated the enzymatic biodegradation of PET at an atomic level using molecular dynamics simulations. Two hydrolases, Ideonella sakaiensis 201-F6 and leaf-branch compost cutinase, showed degradation activity towards PET. The study revealed a characteristic four-step degradation pathway for both enzymes, with LCC-ICCG variant outperforming PETase possibly due to its ability to work at higher temperatures and its intrinsic relationship with the crystallinity grade of the polymer.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
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
Chemistry, Physical
Severin Polonius, Oleksandra Zhuravel, Brigitta Bachmair, Sebastian Mai
Summary: We present a theoretical framework, called the linear vibronic coupling/molecular mechanics (LVC/MM) method, for embedding a hybrid linear vibronic coupling model electrostatically into a molecular mechanics environment. Electrostatic embedding is achieved through the computation of interactions between environment point charges and distributed multipole expansions. By testing with thioformaldehyde in water, we demonstrate that LVC/MM can accurately reproduce the solvation structure and energetics of rigid solutes.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2023)
Review
Chemistry, Multidisciplinary
Katja-Sophia Csizi, Markus Reiher
Summary: Quantum mechanics/molecular mechanics (QM/MM) hybrid models are used to study chemical phenomena in complex molecular environments. While this approach allows for large system sizes at moderate computational costs, constructing the models manually can be tedious. Therefore, developing automated procedures for QM/MM model construction is desired. This article reviews the current state of QM/MM modeling with a focus on automation, covering MM model parametrization, QM region selection, and embedding schemes.
WILEY INTERDISCIPLINARY REVIEWS-COMPUTATIONAL MOLECULAR SCIENCE
(2023)
Article
Multidisciplinary Sciences
Andrew H. Laszlo, Jonathan M. Craig, Momcilo Gavrilov, Ramreddy Tippana, Ian C. Nova, Jesse R. Huang, Hwanhee C. Kim, Sarah J. Abell, Mallory deCampos-Stairiker, Jonathan W. Mount, Jasmine L. Bowman, Katherine S. Baker, Hugh Higinbotham, Dmitriy Bobrovnikov, Taekjip Ha, Jens H. Gundlach
Summary: In this study, the kinetics of superfamily 1 helicase PcrA during DNA translocation and unwinding were investigated using SPRNT technique. The results show that the underlying DNA sequence strongly influences the kinetics of translocation and unwinding.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Zhaoxi Sun, Zhirong Liu
Summary: The study explores indirect free energy simulation methods at quantum mechanics and molecular mechanics levels, as well as attempts to optimize multi-scale treatment by changing the region for electronic structure calculations. The numerical tests show that the estimates from the indirect nonequilibrium perturbation framework are almost identical to the direct results, while the indirect equilibrium estimates deviate from the direct references.
ADVANCED THEORY AND SIMULATIONS
(2021)
Article
Chemistry, Physical
Yuzhuang Fu, Binju Wang, Zexing Cao
Summary: Detailed mechanisms for the chemical steps involved in the biodegradation of 2-oxoadipate (2OA) by HglS enzyme have been explored using MD simulations and QM/MM calculations. The study reveals the presence of two coordination modes of the Fe(IV)-oxo species, with the proximal mode responsible for C-H bond activation. Additionally, residues in the second coordination sphere play a crucial role in substrate binding and facilitate the ferryl-flip, leading to the proximal Fe(IV)-oxo conformation ideal for C-H bond activation.
JOURNAL OF CATALYSIS
(2023)
Article
Chemistry, Multidisciplinary
Guojin Zhang, Daniel Morrison, Guochen Bao, Haibo Yu, Chang Won Yoon, Taekyong Song, Jihye Lee, Alison T. Ung, Zhenguo Huang
Summary: A new amine-borane system with reversible dehydrogenation and regeneration at room temperature has been discovered, producing unique dehydrogenation products with a distinct cyclic structure that can be easily converted back to the original amine-borane. This finding may pave the way for the discovery of new amine-boranes with potential applications as hydrogen storage materials.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Inorganic & Nuclear
Wei-Guo Jia, Xue-Ting Zhi, Xiao-Dong Li, Jun-Peng Zhou, Rui Zhong, Haibo Yu, Richmond Lee
Summary: A mild and environmentally friendly method was reported for synthesizing half-sandwich ruthenium complexes through the Wittig reaction using phosphorus ylide mechanochemically. The synthesized complexes exhibited high catalytic activity in the transfer hydrogenation of ketones without the need for harsh reaction conditions and organic solvents. Density functional theory was used to propose a mechanism for the transfer hydrogenation process, highlighting the importance of the labile p-cymene ligand in modulating catalyst reactivity.
INORGANIC CHEMISTRY
(2021)
Article
Chemistry, Organic
Jayden J. Gaston, Andrew J. Tague, Jamie E. Smyth, Nicholas M. Butler, Anthony C. Willis, Nico van Eikema Hommes, Haibo Yu, Timothy Clark, Paul A. Keller
Summary: The deprotection of chiral 1,2-bis(tosylamides) to their corresponding 1,2-diamines is mostly unsuccessful under standard conditions. However, a new methodology using Mg/MeOH with steric additions allows the facile synthesis of 1,2-diamines in 78-98% yields. These results are rationalized through density functional theory and the examination of inner and outer-sphere reduction mechanisms.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Review
Chemistry, Physical
Huong T. T. Ta, Nam Tran, A. Kiet Tieu, Hongtao Zhu, Haibo Yu, Thi D. Ta
Summary: Recent years have seen an acceleration in research on tribochemical reactions in the field of tribology, with atomic modeling increasingly contributing to the understanding of mechanistic insights and interpretation of frictional outcomes. Efforts have been made to develop simulation codes and models to make simulations closer to practical tribotests with reasonable computational expense. By simulations and modeling, investigations have been conducted on tribochemical reactions and physical/chemical interactions in tribosystems.
JOURNAL OF PHYSICAL CHEMISTRY C
(2021)
Article
Chemistry, Physical
V. S. Sandeep Inakollu, Haibo Yu
Summary: This study investigates the impact of nuclear quantum effects on the vibrational spectra of deprotonated serine using TRPMD simulations. The conformational space analysis and characterization of high-frequency vibrational bands reveal differences between classical MD and TRPMD simulations, particularly at lower temperatures. The hydrogen bond strength and free energy profiles also show variation between the two simulation methods.
STRUCTURAL DYNAMICS-US
(2021)
Article
Chemistry, Medicinal
Nehad S. El Salamouni, Benjamin J. Buckley, Longguang Jiang, Mingdong Huang, Marie Ranson, Michael J. Kelso, Haibo Yu
Summary: The study suggests that residue 99 is a key contributor to the species selectivity of human and mouse uPA inhibitors, with the hexamethylene ring potentially affecting this selectivity by expelling a water molecule, thus influencing the interpretation of data from cancer models.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Biophysics
Nehad S. El Salamouni, Benjamin J. Buckley, Marie Ranson, Michael J. Kelso, Haibo Yu
Summary: This review provides an overview of different classes of uPA inhibitors, their binding interactions with uPA, and their inhibitory potencies. The review also highlights the species selectivity issues of recently described derivatives.
BIOPHYSICAL REVIEWS
(2022)
Article
Chemistry, Organic
Richmond Lee, Chi Bong Eric Chao, Xu Ban, Siu Min Tan, Haibo Yu, Christopher J. T. Hyland, Choon-Hong Tan
Summary: Density functional theory (DFT) was used to predict the mechanism for constructing congested quaternary-quaternary carbon(sp(3))-carbon(sp(3)) bonds in a pentanidium-catalyzed substitution reaction. Computational mechanistic studies revealed that sterically congested substrates prefer the S(N)2X manifold over S(N)2, and different halides as leaving groups showed reactivity in the order of I > Br > Cl > F. The catalyst screening suggested that pentanidium is still the choice for S(N)2X C-C bond formation.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Yan Dai, Xin Zhang, Yongfeng Liu, Haibo Yu, Wei Su, John Zhou, Qing Ye, Zhenguo Huang
Summary: This study reports the first synthesis and characterization of 1,6;2,3-bis-BN cyclohexane, which contains two adjacent BN pairs. This compound exhibits higher reactivity and hydrogen storage capability compared to its isomeric bis-BN cyclohexane.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Biochemistry & Molecular Biology
Guangjian Zhao, Xiaochun Liu, Suyun Wang, Zhongyue Bai, Siyu Zhang, Yifan Wang, Haibo Yu, Ximing Xu
Summary: This study identifies compounds that can inhibit SARS-CoV-2 PLpro through modeling and molecular docking, and confirms the activity of four of these compounds in vitro. These findings provide a starting point for further optimization of PLpro inhibitors.
CHEMICAL BIOLOGY & DRUG DESIGN
(2022)
Article
Chemistry, Physical
Mackenzie Taylor, Haibo Yu, Junming Ho
Summary: In this study, various solvent models were used to predict the rate constants of SN2 reactions in different solvents. The results showed that predicting rate constants in organic solvents is not necessarily more challenging than in water, and among the continuum solvent models, the ADF-COSMO-RS model performed the best in predicting absolute rate constants.
JOURNAL OF PHYSICAL CHEMISTRY B
(2022)
Article
Chemistry, Multidisciplinary
Junbo Chen, Haibo Yu, Davin Tan, Richmond Lee
Summary: The feasibility of various guanidine-based compounds as biomimetic hydride was assessed using Density Functional Theory (DFT). The results suggested that tricyclic pentanidine hydrides could be potential candidates for reducing CO2 to HCOO- and can be regenerated electrochemically, demonstrating a recyclable and sustainable method for metal-free electrochemical reduction of CO2.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Organic
Xia Song, Kelin Wang, Lian Xue, Haibo Yu, Xinying Zhang, Richmond Lee, Xuesen Fan
Summary: This study presents a coupling partner-dependent unsymmetrical C-H bond functionalization of N-phenoxyacetamides, leading to the formation of sophisticated spirocyclic scaffolds. The reactions with diazopyrazolones and diazooxindoles result in the formation of spiropyrazolonyl indazoles and bispirooxindoyl dihydrobenzofurans, respectively. These transformations provide effective strategies for the synthesis of spiroheterocyclic skeletons and demonstrate unprecedented reaction modes of N-phenoxyacetamides with cyclic diazo compounds.
ORGANIC CHEMISTRY FRONTIERS
(2022)
Article
Chemistry, Multidisciplinary
Danielle Skropeta, Christopher Dobie, Andrew P. Montgomery, Harrison Steele, Remi Szabo, Haibo Yu
Summary: Sialic acid plays a crucial role in cell-cell communication, with sialyltransferases involved in its biosynthesis upregulated in various cancers. Research groups are exploring inhibiting sialylation as a new cancer treatment strategy, but issues around selectivity, synthetic accessibility, and cell permeability need to be addressed for small molecule ST inhibitors to progress into the clinic.
AUSTRALIAN JOURNAL OF CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Christopher Dobie, Andrew P. Montgomery, Remi Szabo, Haibo Yu, Danielle Skropeta
Summary: This study introduces a new generation of 1,2,3-triazole-linked sialyltransferase inhibitors, demonstrating increased potency for phosphonate bearing compounds. Promising as a class of synthetically accessible ST inhibitors, further investigation is warranted for triazole-linked compounds bearing phosphonate.
RSC MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Ankita Chadda, Alexander G. Kozlov, Binh Nguyen, Timothy M. Lohman, Eric A. Galburt
Summary: In this study, it was found that the DNA damage response in Mycobacterium tuberculosis differs from well-studied model bacteria. The DNA repair helicase UvrD1 in Mtb is activated through a redox-dependent process and is closely associated with the homo-dimeric Ku protein. Additionally, Ku protein is shown to stimulate the helicase activity of UvrD1.
JOURNAL OF MOLECULAR BIOLOGY
(2024)