Tong Zhu

Tong Zhu
East China Normal University | ECNU · School of Chemistry and Molecular Engineering

PhD

About

91
Publications
8,938
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1,350
Citations
Additional affiliations
July 2017 - present
East China Normal University
Position
  • Professor (Associate)
June 2015 - June 2017
East China Normal University
Position
  • Professor (Associate)

Publications

Publications (91)
Article
Full-text available
Complex biomolecular circuits enabled cells with intelligent behaviour to survive before neural brains evolved. Since DNA computing was first demonstrated in the mid-1990s, synthetic DNA circuits in liquid phase have been developed as computational hardware to perform neural network-like computations that harness the collective properties of comple...
Preprint
Accurate predicting thermodynamics and kinetics of DNA molecules are important for designing oligonucleotides in biotechnological applications, but current models in use are not accurate enough. Here, we propose a model combining quantum chemical calculations and convolutional neural networks (QCM) to predict the free energies of DNA duplexes and r...
Article
The product branching ratio between different products in multichannel reactions is as important as the over-all rate of reaction, both in terms of practical applications ( e.g. models of combustion or atmosphere chemistry) in understanding the fundamental mechanisms of such chemical reactions. A global ground state potential energy surface for the...
Article
CL-20 (2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane, also known as HNIW) is one of the most powerful energetic materials. However, its high sensitivity to environmental stimuli greatly reduces its safety and severely limits its application. In this work, ab initio based neural network potential (NNP) energy surfaces for both β-CL-20 a...
Article
Direct nonoxidative conversion of methane to ethylene, aromatics and hydrogen has been recognized as an attractive utilization of natural gas, but qualified catalyst faces huge challenges. Most catalysts reported for this reaction are deactivated fast by carbon deposition. Herein, we demonstrated an active, selective and stable molten tungsten-indi...
Article
Due to unknown pathogenesis and unidentified drug target, no drug for the treatment of osteosarcoma (OS) has been launched to the market. Herein, thiazolidinone 1a was discovered as a hit compound by phenotypic screening with an in-house patrimonial collection of structural diversity. The following SAR (Structure-Activity Relationship) study afford...
Preprint
Complex biomolecular circuits enable cells with intelligent behavior for survival before neural brains evolved. Synthesized DNA circuits in liquid phase developed as computational hardware can perform neural-network-like computation that harness the collective properties of complex biochemical systems, however the scaling up in complexity remains c...
Article
Full-text available
Prenylated indole alkaloids featuring spirooxindole rings possess a 3R or 3S carbon stereocenter, which determines the bioactivities of these compounds. Despite the stereoselective advantages of spirooxindole biosynthesis compared with those of organic synthesis, the biocatalytic mechanism for controlling the 3R or 3S-spirooxindole formation has be...
Article
Full-text available
The development of accurate and efficient potential energy functions for the molecular dynamics simulation of metalloproteins has long been a great challenge for the theoretical chemistry community. An artificial neural network provides the possibility to develop potential energy functions with both the efficiency of the classical force fields and...
Article
Ab initio CCSD(T)/CBS//ωB97X-D/6-311+G(d,p) calculations of the C6H6N potential energy surface were performed to investigate the reaction mechanism underlying the reaction of atomic nitrogen (2D) with benzene. Thereafter, Rice-Ramsperger-Kassel-Marcus (RRKM) calculations of reaction rate constants and product branching ratios were performed under s...
Article
Full-text available
We develop a fragment-based ab initio molecular dynamics (FB-AIMD) method for efficient dynamics simulation of the combustion process. In this method, the intermolecular interactions are treated by a fragment-based many-body expansion in which three- or higher body interactions are neglected, while two-body interactions are computed if the distance...
Article
Recently, the RNA aptamers activating small-molecule fluorophores have been successfully applied to tag and track RNAs in vivo. It is of significance to investigate the molecular mechanism of the fluorophore-RNA aptamer bindings at the atomic level for seeking possible pathway to enhance fluorescence efficiency of fluorophores. In this work, multip...
Preprint
In recent years, the use of deep learning (neural network) potential energy surface (NNPES) in molecular dynamics simulation has experienced explosive growth as it can be as accurate as quantum chemistry methods while being as efficient as classical mechanic methods. However, the development of NNPES is highly non-trivial. In particular, it has bee...
Preprint
p> G-Quadruplexes (GQs), folded by guanine-rich nucleic acid sequences , involve in gene expression processes and closely associated with the formation of tumors. So far, GQ has drawn widespread attention for its notable application of serving as potential anti-cancer target. Recently, theoretical studies for GQs have achieved significant progress,...
Article
A rational design strategy was proposed to improve the efficient utilization of alternative biomimetic cofactor by P450 BM3 enzyme.
Article
Reactive molecular dynamics (MD) simulation is a powerful tool to study the reaction mechanism of complex chemical systems. Central to the method is the potential energy surface (PES) that can describe the breaking and formation of chemical bonds. The development of both accurate and efficient PES has attracted significant effort in the past 2 deca...
Article
Never in mitosis (NIMA) related kinase 2 (Nek2) is involved in multiple cellular processes such as cell cycle checkpoint regulation, cell division, DNA damage response and cell apoptosis. Nek2 has been reported to be overexpressed in various tumors and correlated with poor prognosis. Herein, a series of imidazo[1,2-a] pyridines Nek2 inhibitors were...
Preprint
p>Artificial neural network provides the possibility to develop molecular potentials with both the efficiency of the classical molecular mechanics and the accuracy of the quantum chemical methods. In this work, we developed ab initio based neural network potential (NN/MM-RESP-MBG) to perform molecular dynamics study for metalloproteins. The interac...
Article
Full-text available
Combustion is a complex chemical system which involves thousands of chemical reactions and generates hundreds of molecular species and radicals during the process. In this work, a neural network-based molecular dynamics (MD) simulation is carried out to simulate the benchmark combustion of methane. During MD simulation, detailed reaction processes...
Article
Blockage of p53-MDM2 protein-protein interaction has long been a promising strategy of drug development for cancers with wild type p53. In this study, we report a new p53-MDM2 interaction inhibitor, CYZ2017, which could induce p53 nuclear translocation and possess p53-dependent anti-proliferation activity in a range of cancer cells. CYZ2017 treatme...
Article
A method for accurate calculation of reorganization free energy of an explicit solvent solvating a solute molecule is presented. The method relies upon the knowledge of solvation free energy, either known from experimental measurement or is accurately calculated. An important part of this approach lies in the calculation of entropy in solute-solven...
Preprint
Full-text available
div> Reactive molecular dynamics (MD) simulation is a powerful tool to study the reaction mechanism of complex chemical systems. Central to the method is the potential energy surface (PES) that can describe the breaking and formation of chemical bonds. The development of PES of both accurate and efficent has attracted significant effort in the pa...
Article
Regarding CH3OH⁺ and CH3OH⁺⁺, theoretical calculations have used a variety of methods to describe geometric structures and potential energy surfaces. Rice–Ramsperger–Kassel–Marcus (RRKM) theory has been applied to compute the rate constants and product branching ratios of various channels on potential energy surfaces. The dissociate ions produced f...
Article
Ab initio CCSD(T)/CBS//B3LYP/6-311G(d,p) calculations of the potential energy surface for possible dissociation channels of HOC2H3F, as well as Rice-Ramsperger-Kassel-Marcus (RRKM) calculations of rate constants, were carried out, in order to predict statistical product branching ratios in dissociation of HOC2H3F at various internal energies. The m...
Preprint
Full-text available
Combustion is a kind of important reaction that affects people's daily lives and the development of aerospace. Exploring the reaction mechanism contributes to the understanding of combustion and the more efficient use of fuels. Ab initio quantum mechanical (QM) calculation is precise but limited by its computational time for large-scale systems. In...
Preprint
Full-text available
Understanding and prediction of the chemical reactions are fundamental demanding in the study of many complex chemical systems. Reactive molecular dynamics (MD) simulation has been widely used for this purpose as it can offer atomic details and can help us better interpret chemical reaction mechanisms. In this study, two reference datasets were con...
Article
Reactive molecular dynamics (MD) simulation makes it possible to study the reaction mechanisms of complex reaction systems at the atomic level. However, the analysis of the MD trajectories which contain thousands of species and reaction pathways has become a major obstacle to the application of reactive MD simulation in large-scale systems. Here, w...
Article
This study examined the reaction mechanisms of singlet (rhombic) and triplet (linear) C4 with acetylene by using accurate ab initio CCSD(T)/CBS//B3LYP/6-311G(d,p) calculations followed by a kinetic analysis of various reaction pathways and computations of relative product yields in combustion and planetary atmospheres. These calculations were combi...
Article
Methyl glycolate (MG) is a versatile platform molecule to produce numerous important chemicals and materials, especially new-generation biocompatible and biodegradable polyglycolic acid. In principle, it can be massively produced from syngas (CO + H2) via gas-phase hydrogenation of CO-derived dimethyl oxalate (DMO), but the groundbreaking catalyst...
Article
Type III phosphatidylinositol 4 kinases (PI4KIIIs) are essential enzymes that relating to the replication of multiple RNA viruses. Understanding the interaction mechanism of molecular compounds with the alpha and beta isoforms of PI4KIII (PI4KIIIα and PI4KIIIβ) is of significance in the development of inhibitors which can bind to these two enzymes...
Article
Artificial neural network provides the possibility to develop molecular potentials with both the efficiency of the classical molecular mechanics and the accuracy of the quantum chemical methods. Here, we develop an ab initio based neural network potential (NN/MM-RESP) to perform molecular dynamics study of zinc ion in liquid water. In this approach...
Article
This work compares pyrolysis reactions of a 3-component surrogate model and a 4-component surrogate model of RP-3 aviation fuel by ReaxFF molecular dynamics simulation method. To evaluate the reactivity of the two RP-3 surrogate models, a multi-component baseline model that consists of 45 components was constructed as a representative of real RP-3...
Article
The FK506-binding protein 51 (FKBP51) is a cochaperone that modulates the signal transduction of steroid hormone receptors and has been involved in prostate cancer, indicating that FKBP51 is an attractive target of drug design curing the related cancers. In this work, multiple short molecular dynamics (MSMD) simulations are combined with MM-GBSA me...
Article
Full-text available
Riboswitches can regulate gene expression by direct and specific interactions with ligands and have recently attracted interest as potential drug targets for antibacterial. In this work, molecular dynamics (MD) simulations, free energy perturbation (FEP) and molecular mechanics generalized Born surface area (MM-GBSA) methods were integrated to prob...
Article
Injectable hydrogels are increasingly being used as scaffolds for in situ tissue engineering and wound healing. Most of these injectable hydrogels are made from polymers and there are fewer examples of such soft materials made via self-assembly of low-molecular weight gelators. We report the room temperature synthesis of a functional hydrogel forme...
Article
Insight into the binding mechanisms of inhibitors of MDM2 are of significance for the development of drugs targeting the p53-MDM2 protein complex. In this work, an MD simulation, MM-GBSA, and SIE methods are combined to study the interaction details of MDM2 with three small nutlins. Structural analyses show that inhibitor binding can weaken the str...
Article
CDK2 can be used as an attractive target for development of efficient inhibitors curing multiple disease relating with CDK2. In this work, molecular dynamics (MD) simulations and binding free energy calculations were coupled to probe conformational changes of CDK2 due to inhibitor associations and binding mechanisms of inhibitors PM1, FMD and X64 t...
Preprint
This study examined the formation mechanisms of singlet (rhombic) and triplet (linear) C4 with acetylene by using accurate ab initio CCSD(T)/cc-pVTZ/B3LYP/6-311G(d,p) calculations, followed by a kinetic analysis of various reaction pathways and computations of relative product yields in combustion and planetary atmospheres. These calculations were...
Preprint
The equilibrium geometry and 48 vibrational normal-mode frequencies of the neutral and cationic ground state and the cationic first excited states of naphthalene isomers were calculated and characterized in the adiabatic representation by using the complete active space self-consistent field (CASSCF) and second order perturbation theory (CASPT2). P...
Article
Full-text available
Inhibition of aberrant Hedgehog (Hh) pathway had been proved to be a promising therapeutic intervention in cancers like basal cell carcinoma (BCC), medulloblastoma (MB), and so on. Two drugs (Vismodegib, Sonidegib) were approved to treat BCC and more inhibitors are in clinical investigation. However, the adverse effects and drug resistance restrict...
Article
Full-text available
Recently, CDK2 has been a promising target of drug development for the treatment of the myriad of various human diseases. Molecular dynamics (MD) simulations are integrated with an efficient interaction entropy method to probe the effect of substitutions at S1 and S2 positions of the aminothiazole hinge-binding scaffold (1-{4-amino-2-(alkyl(o-aryl)...
Preprint
Full-text available
Reactive molecular dynamics (MD) simulation makes it possible to study the reaction mechanisms of complex reaction systems at the atomic level. However, the analysis of the MD trajectories which contain thousands of species and reaction pathways has become a major obstacle to the application of reactive MD simulation in large-scale systems. Here, w...
Article
Aggregation of the misfolded scrapie prion protein (PrPSc) is known to cause neurodegenerative diseases. In this paper, we have investigated the stability of PrPC by combining coarse-grained model and all-atom molecular simulations. Our results show that the unfolding of PrPC starts from the opening of the folded domain with α1 moving away from α2α...
Article
I84V mutation in HIV-1 protease (PR) has produced drug resistance on multiple inhibitors. Thermodynamic integration (TI), solvated interaction energy (SIE) and dynamic analysis were applied to comparatively probe drug-resistant mechanisms of I84V mutation toward four inhibitors. Dynamic analysis suggests that in the I84V mutants the flaps of PR are...
Article
Full-text available
In this study, the automated fragmentation quantum mechanics/molecular mechanics (AF-QM/MM) method was applied for NMR chemical shift calculations of protein-ligand complexes. In the AF-QM/MM approach, the protein binding pocket is automatically divided into capped fragments (within ~200 atoms) for density functional theory (DFT) calculations of NM...
Article
Full-text available
A force balanced generalized molecular fractionation with conjugate caps (FB-GMFCC) method is proposed for ab initio molecular dynamic simulation of proteins. In this approach, the energy of the protein is computed by a linear combination of the QM energies of individual residues and molecular fragments that account for the two-body interaction of...
Article
Full-text available
An efficient computational approach for modeling protein electrostatic is developed according to static point-charge model distributions based on the linear-scaling EE-GMFCC (electrostatically embedded generalized molecular fractionation with conjugate caps) quantum mechanical (QM) method. In this approach, the Electrostatic-Potential atomic charge...
Article
Full-text available
The reaction mechanisms of one-pot conversion of carbon dioxide, ethylene oxide and amines to 3-substituted-2-oxazolidinones catalyzed by the binary ionic liquids of BmimBr and BmimOAc were investigated using DFT methods. In this work, we focus on exploring how the different substituents in amines affect the yields of 3-substituted-2-oxazolidinones...
Article
Water molecules can serve as proton shuttles for proton transfer in the C-H bond insertion reactions catalyzed by transition metal complexes. Recently, the control experiments performed for C-H bond insertion of phenol and anisol by gold carbenes show that large discrepancy exists in the yields of hydrogenated and deuterated products. Thus, we cond...
Article
In this work, we develop a novel methodology for designing electrochemical biosensors with both current and potential signal outputs for simultaneous determination of two important species in the live systems. By designing a new molecule, Hemin-aminoferrocene (Hemin-Fc), we create a single electrochemical biosensor for simultaneous quantification o...
Article
In this work, we develop a novel methodology for designing electrochemical biosensors with both current and potential signal outputs for simultaneous determination of two important species in the live systems. By designing a new molecule, Hemin-aminoferrocene (Hemin-Fc), we create a single electrochemical biosensor for simultaneous quantification o...
Article
Glucose and pH are two important indicators of diabetes mellitus. However, their dynamic changes at the same time in brain are still not clear, mainly due to a lack of a single biosensor capable of simultaneous quantification of two species in a live rat brain. In this work, a selective and sensitive ratiometric electrochemical biosensor was develo...
Article
We report direct folding study of seven helical proteins (2I9M, Trpcage, 1WN8, C34, N36, 2KES, 2KHK) ranging from 17 to 53 amino acids through standard molecular dynamics simulation using a recently developed polarizable force field-Effective Polarizable Bond (EPB) method. The backbone RMSDs, radius of gyrations, native contacts and native helix co...
Article
We tested the ability of some current AMBER force fields, namely, AMBER03, AMBER99SB, AMBER99SB-ildn, AMBER99SB-nmr, AMBER12SB, AMBER14SB, and AMBER14ipq, with implicit solvent model in reproducing the folding behavior of two peptides by REMD simulations. AMBER99SB-nmr force field provides the most reliable performance. After a novel polarized hydr...
Article
Molecular dynamics simulations in explicit water are carried out to study the binding of six inhibitors to HIV-1 protease (PR) for up to 700 ns using the standard AMBER force field and polarized protein-specific charge (PPC). PPC is derived from quantum mechanical calculation for protein in solution and therefore it includes electronic polarization...
Article
We present herein the discovery and development of novel and potent Nek2 inhibitors with distinctive in vitro and in vivo antitumor activity based on an imidazo[1,2-a]pyridine scaffold. Our studies identified a nonlinear SAR for activity against both Nek2 and cancer cells. Bioisostere and structure-based design techniques were employed to identify...
Article
Full-text available
Background Overexpression of Aurora A and B has been reported in a wide range of tumor types, including gastric cancer. Anti-angiogenesis has been considered as an important therapeutic modality in advanced gastric cancer. Here we identified a novel compound TY-011 with promising antitumor activity by targeting mitotic kinases (Aurora A and B) and...
Article
Protein tyrosine phosphatase 1B (PTP1B) has been proposed to be an effective target for the treatment of both type II diabetes and obesity. However, no PTP1B inhibitor has come into clinic application. Herein, we report mixed 3,3'-bisindoles as novel PTP1B inhibitors with low micromole-ranged inhibitory activity. The best active compound 9f inhibit...
Article
H, ¹³C and ¹⁵N NMR chemical shift calculations on RNAs were performed using the automated fragmentation quantum mechanics/molecular mechanics (AF-QM/MM) approach. Systematic investigation was carried out to examine the influence of density functionals, force fields, ensemble average and explicit solvent molecules on NMR chemical shift calculations....
Article
Full-text available
NEK2 is a conserved mitotic regulator critical for cell cycle progression. Aberrant expression of NEK2 has been found in a variety of human cancers, making it an attractive molecular target for the design of novel anticancer therapeutics. In the present study, we have identified a novel compound MBM-5, which was found to bind to NEK2 with high affi...