THE INFLUENCE OF SUBSTITUENT ELECTRONIC EFFECT ON ETHYLENE OLIGOMERIZATION ACTIVITIES OF BIS(IMINO)PYRIDYL Fe(Ⅱ) CATALYSTS:A COMBINED MOLECULAR MECHANICS AND CHARGE EQUILIBRATION METHOD

Bis(imino)pyridyl Fe(Ⅱ) complexes are important catalysts in ethylene oligomerization for preparingα-olefins. The metal net charge-activity relationship of bis(imino)pyridyl Fe(Ⅱ) complexes was investigated by molecular mechanics (MM) and net charge equilibration(QEq) method with modified Dreiding force field.It was found that metal net charge was in reverse ratio to ethylene oligomerization activity.Electron-donor substituents with less steric hindrance to the central metal were favorable to Fe complex act...

QM/MM Study on Enzymatic Mechanism in Sinigrin Biosynthesis

As the major and abundant type of glucosinolates(GL)in plants,sinigrin has potential functions in promoting health and insect defense.The final step in the biosynthesis of sinigrin core structure is highly representative in GL compounds,which corresponds to the process from 3-methylthiopropyl ds-GL to 3-methylthiopropyl GL catalyzed by sulfotransferase(SOT).However,due to the lack of the crystallographic structure of SOT complexed with the 3-methylthiopropyl GL,little is known about this sulfonation process.Fortunately,the crystal structure of SOT 18 from Arabidopsis thaliana(At SOT18)containing the substance(sinigrin)similar to 3-methylthiopropyl GL has been determined.To understand the enzymatic mechanism,we employed molecular dynamics(MD)simulation and quantum mechanics combined with molecular mechanics(QM/MM)methods to study the conversion from ds-sinigrin to sinigrin catalyzed by AtSOT18.The calculated results demonstrate that the reaction occurs through a concerted dissociative mechanism.Moreover,Lys93,Thr96,Thr97,Tyr130,His155,and two enzyme peptide chains(Pro92-Lys93 and Gln95-Thr96-Thr97)play a role in positioning the substrates and promoting the catalytic reaction by stabilizing the transition state geometry.Particularly,His155 acts as a catalytic base while Lys93 acts as a catalytic acid in the reaction process.The presently proposed concerted dissociative mechanism explains the role of At SOT18 in sinigrin biosynthesis,and could be instructive for the study of GL biosynthesis catalyzed by other SOTs.

Perspective for aggregation-induced delayed fluorescence mechanism:A QM/MM study

To enhance the potential application of thermally activated delayed fluorescence(TADF)molecular materials,new functions are gradually cooperated to the TADF molecules.Aggregation induced emission can effectively solve the fluorescence quenching problem for TADF molecules in solid phase,thus aggregation-induced delayed fluorescence(AIDF)molecules were recently focused.Nevertheless,their luminescent mechanisms are not clear enough.In this work,excited state properties of an AIDF molecule DMF-BP-DMAC[reported in Chemistry-An Asian Journal 14828(2019)]are theoretically studied in tetrahydrofuran(THF)and solid phase.For consideration of surrounding environment,the polarizable continuum method(PCM)and the combined quantum mechanics and molecular mechanics(QM/MM)method were applied for solvent and solid phase,respectively.Due to the increase of the transition dipole moment and decrease of the energy difference between the first single excited state(S1)and the ground state(S0),the radiative rate is increased by about 2 orders of magnitude in solid phase.The energy dissipation of the non-radiative process from S1 to S0 is mainly contributed by low-frequency vibrational modes in solvent,and they can be effectively suppressed in aggregation,which may lead to a slow non-radiation process in solid phase.Both factors would induce enhanced luminescence efficiency of DMF-BP-DMAC in solid phase.Meanwhile,the small energy gap between S1 and triplet excited states results in high reverse intersystem crossing(RISC)rates in both solvent and solid phase.Therefore,TADF is confirmed in both phases.Aggregation significantly influences both the ISC and RISC processes and more RISC channels are involved in solid state.The enhanced delayed fluorescence should be induced by both the enhanced fluorescent efficiency and ISC efficiency.Our calculation provides a reasonable explanation for experimental measurements and helps one to better understand the luminescence mechanism of AIDF molecules.

Molecular Dynamics Study on Mechanical Properties in the Structure of Self-Assembled Quantum Dot

Stress and strain in the structure of self-assembled quantum dots constructed in the Ge/Si(001) system is calculated by using molecular dynamics simulation. Pyramidal hut cluster composed of Ge crystal with {105} facets surfaces observed in the early growth stage are computationally modeled. We calculate atomic stress and strain in relaxed pyramidal structure. Atomic stress for triplet of atoms is approximately defined as an average value of pairwise (virial) quantity inside triplet, which is the product of vectors between each two atoms. Atomic strain by means of atomic strain measure (ASM) which is formulated on the Green’s definition of continuum strain. We find the stress (strain) relaxation in pyramidal structure and stress (strain) concentration in the edge of pyramidal structure. We discuss size dependency of stress and strain distribution in pyramidal structure. The relationship between hydrostatic stress and atomic volumetric strain is basically linear for all models, but for the surface of pyramidal structure and Ge-Si interface. This means that there is a reasonable correlation between atomic stress proposed in the present study and atomic strain measure, ASM.

Microwave-assisted synthesis,anticonvulsant activity and quantum mechanical modelling of N-(4-bromo-3-methylphenyl) semicarbazones

Objective: To study the effect of halo substitution on disubstituted aryl semicarbazones on the anticonvulsant potential and model the activity based on quantum mechanics. Methods: A series of twenty-six compounds of N4-(4-bromo-3-methylphenyl) semicarbazones were synthesized and evaluated for the anticonvulsant activity in the maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ) seizure threshold tests. Some potential compounds were also tested in the subcutaneous strychnine (scSTY) and subcutaneous picrotoxin (scPIC) seizure threshold tests. The synthesized compounds were tested for behavioral impairment and CNS (central nervous system) depression in mice. Quantum mechanical modelling was carried out on these compounds to gain understanding on the structural features essential for activity. Results: Some compounds possessed broad spectrum anticonvulsant activity as indicated by their effect in pentylenetetrazole, strychnine, picrotoxin and maximal electro- shock seizures models in resemblance to other aryl semicarbazone derivatives reported earlier. The higher the difference in HOMO (highest occupied molecular orbital) and LUMO (lowest unoccupied molecular orbital) energy levels was, the greater was the activity profile. Conclusion: The pharmacophoric requirements for compounds to exhibit anticonvulsant activity that includes one aryl unit in proximity to a hydrogen donor-acceptor domain and an electron donor have been justified with the molecular orbital surface analysis of the synthesized compounds.

Molecular Hydrogen Storage in Spherophanes： A Molecular Mechanic Investigation

At the molecular mechanic level, the capability of a set of 24 molecular cage-like structures, the spherophanes, to store hydrogen molecules has been studied. Two main factors have been found to govern their storage capacity： the volume of their cavity and the potential energy barriers at the different openings at the surface of the cage. Calculations have shown that 13H2 molecules could be stored inside the thiaspherophane, Th4S, whose mean radius is 10A and the resulting complex （H2）I3@Th4S is found to be stable. The results show that it would be very difficult to store more than 2H2 inside the smallest spherophane, Sp4, whose mean radius is 7.7A. The mean intermolecular distance Hz-Hz and the mean bond length H-H have been found to decrease when the number of imprisoned hydrogen molecules increases. It has also been found that the encapsulated H2 molecules form clusters of different symmetries on which the formation energy depends strongly. Even with 13H2 molecules inside Th4S, the weight percentage is still small, 2.57%. The largest obtained wt% is 3.22% in the case of Th5S（CH3）10.

Exploring unbinding mechanism of drugs from SERT via molecular dynamics simulation and its implication in antidepressants

The human serotonin transporter(SERT)terminates neurotransmission by removing serotonin from the synaptic cleft,which is an essential process that plays an important role in depression.In addition to natural substrate serotonin,SERT is also the target of the abused drug cocaine and,clinically used antidepressants,escitalopram,and paroxetine.To date,few studies have attempted to investigate the unbinding mechanism underlying the orthosteric and allosteric modulation of SERT.In this article,the conserved property of the orthosteric and allosteric sites(S1 and S2)of SERT was revealed by combining the high resolutions of x-ray crystal structures and molecular dynamics(MD)simulations.The residues Tyr95 and Ser438 located within the S1 site,and Arg104 located within the S2 site in SERT illustrate conserved interactions(hydrogen bonds and hydrophobic interactions),as responses to selective serotonin reuptake inhibitors.Van der Waals interactions were keys to designing effective drugs inhibiting SERT and further,electrostatic interactions highlighted escitalopram as a potent antidepressant.We found that cocaine,escitalopram,and paroxetine,whether the S1 site or the S2 site,were more competitive.According to this potential of mean force(PMF)simulations,the new insights reveal the principles of competitive inhibitors that lengths of trails from central SERT to an opening were~18A for serotonin and~22 A for the above-mentioned three drugs.Furthermore,the distance between the natural substrate serotonin and cocaine(or escitalopram)at the allosteric site was~3A.Thus,it can be inferred that the potent antidepressants tended to bind at deeper positions of the S1 or the S2 site of SERT in comparison to the substrate.Continuing exploring the processes of unbinding four ligands against the two target pockets of SERT,this study observed a broad pathway in which serotonin,cocaine,escitalopram(at the S1 site),and paroxetine all were pulled out to an opening between MT1b and MT6a,which may be helpful to understand the dissociation mechanism of antidepressants.

Improving performance of screening MM/PBSA in protein–ligand interactions via machine learning

Accurately estimating protein–ligand binding free energy is crucial for drug design and biophysics, yet remains a challenging task. In this study, we applied the screening molecular mechanics/Poisson–Boltzmann surface area(MM/PBSA)method in combination with various machine learning techniques to compute the binding free energies of protein–ligand interactions. Our results demonstrate that machine learning outperforms direct screening MM/PBSA calculations in predicting protein–ligand binding free energies. Notably, the random forest(RF) method exhibited the best predictive performance,with a Pearson correlation coefficient(rp) of 0.702 and a mean absolute error(MAE) of 1.379 kcal/mol. Furthermore, we analyzed feature importance rankings in the gradient boosting(GB), adaptive boosting(Ada Boost), and RF methods, and found that feature selection significantly impacted predictive performance. In particular, molecular weight(MW) and van der Waals(VDW) energies played a decisive role in the prediction. Overall, this study highlights the potential of combining machine learning methods with screening MM/PBSA for accurately predicting binding free energies in biosystems.

QM/MM方法的研究

从理论上探讨了QM/MM方法在模拟计算生物大分子体系的运用,实践表明这种方法能提高计算结果的精确性,能有效地降低计算成本.

丝组二肽对DNA切割作用的QM-MM研究

运用QM MM方法对丝组二肽切割DNA作用的机理进行了研究 .通过计算得到了丝组二肽与DNA形成多氢键作用的有效分子识别模型及相关分子结构参数 ,从理论上解释了丝组二肽与DNA通过形成五配位磷中间体而使磷酸二酯键发生水解 ,从而使得DNA被切断的作用机理 .

烟酰胺酶催化水解脱氨反应的QM/MM分子动力学模拟

采用QM(PM3)/MM分子动力学(MD)方法模拟了烟酰胺酶催化烟酰胺水解脱氨形成烟碱酸的反应过程.计算结果表明,硫的亲核进攻是整个反应的速率控制步骤.当改变Ala155所在Loop区的位置,在亲核进攻时,底物能够自由旋转,可以加速亲核进攻过程并降低整个催化反应的能垒.讨论了氨分子的离去过程和质子传递过程的相关细节.为烟酰胺酶的定点突变以及脱氨酶的设计提供了有益的参考.

THE COUPLED EFFECTS OF MECHANICAL DEFORMATION AND ELECTRONIC PROPERTIES IN CARBON NANOTUBES

Coupled effects of mechanical and electronic behavior in single walled carbon nanotubes are investigated by using quantum mechanics and quantum molecular dynamics.It is found that external applied electric fields can cause charge polarization and significant geometric deformation in metallic and semi-metallic carbon nanotubes.The electric induced axial tension ratio can be up to 10% in the armchair tube and 8.5% in the zigzag tube.Pure external applied load has little effect on charge distribution,but indeed influences the energy gap.Tensile load leads to a narrower energy gap and compressive load increases the gap.When the CNT is tensioned under an external electric field,the effect of mechanical load on the electronic structures of the CNT becomes significant,and the applied electric field may reduce the critical mechanical tension load remarkably.Size effects are also discussed.

A computational toolbox for molecular property prediction based on quantum mechanics and quantitative structure-property relationship

Chemical industry is always seeking opportunities to efficiently and economically convert raw materials to commodity chemicals and higher value-added chemicalbased products.The life cycles of chemical products involve the procedures of conceptual product designs,experimental investigations,sustainable manufactures through appropriate chemical processes and waste disposals.During these periods,one of the most important keys is the molecular property prediction models associating molecular structures with product properties.In this paper,a framework combining quantum mechanics and quantitative structure-property relationship is established for fast molecular property predictions,such as activity coefficient,and so forth.The workflow of framework consists of three steps.In the first step,a database is created for collections of basic molecular information;in the second step,quantum mechanics-based calculations are performed to predict quantum mechanics-based/derived molecular properties(pseudo experimental data),which are stored in a database and further provided for the developments of quantitative structure-property relationship methods for fast predictions of properties in the third step.The whole framework has been carried out within a molecular property prediction toolbox.Two case studies highlighting different aspects of the toolbox involving the predictions of heats of reaction and solid-liquid phase equilibriums are presented.

Mechanistic, Energetic and Structural Aspects of the Adsorption of Carmustine on the Functionalized Carbon Nanotubes

Using density functional theory, noncovalent interactions and two mechanisms of covalent functionalization of drug carmustine with functionalized carbon nanotube（CNT） have been investigated. Quantum molecular descriptors of noncovalent configurations were studied. It was specified that binding of drug carmustine with functionalized CNT is thermodynamically suitable. NTCOOH and NTCOCl can bond to the NH group of carmustine through OH（COOH mechanism） and Cl（COCl mechanism） groups, respectively. The activation energies, activation enthalpies and activation Gibbs free energies of two pathways were calculated and compared with each other. The activation parameters related to COOH mechanism are higher than those related to COCl mechanism, and therefore COCl mechanism is suitable for covalent functionalization. COOH functionalized CNT（NTCOOH） has more binding energy than COCl functionalized CNT（NTCOCl） and can act as a favorable system for carmustine drug delivery within biological and chemical systems（noncovalent）. These results could be generalized to other similar drugs.

Reaction Mechanism of Actin ATP Hydrolysis Studied by QM/MM Calculations

Actin fibers are an important part of the cytoskeleton,providing vital support for the plasma membrane.This function is driven by its ATPase(ATP:adenosine triphosphate)activity,i.e.,ATP+H_(2)O→ADP+Pi.This seemingly simple reaction has attracted much attention because the hydrolysis of ATP provides energy to support life processes.However,the reaction mechanism of ATP hydrolysis in actin is not clear.In order to gain deep insights into the functions of actin,it is essential to elucidate the reaction mechanism of the actin ATP hydrolysis.In this paper,we have studied the reaction mechanism of the ATP hydrolysis in actin by the combined quantum mechanical and molecular mechanics(QM/MM)calculations.Our results show that 1)bond cleavage of the Pγ—OS of ATP and bond formation between oxygen of the lytic water and Pγatoms take place simultaneously,and this is the rate-limiting step of the hydrolysis;2)the proton on the lytic water transfers to the phosphate to form H_(2)P_(γ)O_(4)−via one bridge water.The energy barrier of the complete reaction is 17.6 kcal/mol(1 kcal=4.184 kJ),which is in high agreement with the experimental value.

应用ABEEM/MM模型研究水分子团簇(H_2O)_n(n=11～16)的性质

应用ABEEM/MM模型计算了较大的水分子团簇(H2O)n(n=11￣16)的各种性质,如:优化的几何构型,氢键个数,结合能,稳定性,ABEEM电荷分布,偶极矩,以及结构参数、平均氢键个数和强度,增加的团簇结合能等.结果表明,从立方体结构到笼状结构的过渡出现在n=12的水分子团簇中,随着类似于笼状结构特点的不断增强,五元环的富集程度有所增加.

原子-键电负性均衡方法融合进分子力场(ABEEM/MM)应用于蛋白质分子(Crambin)模拟

建立应用于多肽和蛋白质模拟的ABEEM/MM浮动电荷力场.利用该模型和参数,对实际蛋白质分子Cramb in(植物种子中的一种小的蛋白质)进行模拟,得到了满意的结果,为其更广泛的应用开辟了道路.

应用ABEEM／MM力场模型研究水分子团簇(H2O)n(n=7～35)的性质

应用ABEEM/MM模型研究和计算了水分子团簇(H2O)n(n=7～35)的各种性质,如:优化的几何构型,氢键个数,结合能,稳定性,ABEEM电荷分布,偶极矩,以及结构参数、平均氢键个数和强度、团簇的递增结合能等,并描述了六聚水区域中所反映的从二维结构(从二聚水到五聚水)到三维结构(n>6的水分子团簇)的过渡,又进一步地预测了从立方体结构到笼状结构的过渡出现在n=12的水分子团簇中,随着类似于笼状结构特点的不断增强,五元环的富集程度有所增加.以上研究不仅系统研究和分析了水团簇的各种性质,而且对比Abini-tio研究和实验结果,进一步验证了ABEEM/MM模型的合理性以及参数的正确性和可转移性.

共轭烯烃的分子几何构型、电子结构和生成热的DMM和AM1、PM3的比较研究

运用Ｄｅｌｆｔ分子力学（ＤＭＭ）力场和程序以及半经验分子轨道ＡＭ１和ＰＭ３方法计算研究了丁二烯、苯、甲苯、联苯、苯乙烯、富烯、、环辛四烯、［２，２］对环烷和菲等１０个共轭烯烃分子的几何构型、电子结构和生成热．ＤＭＭ计算的几何构型和生成热与实验结果相吻合，电荷分布结果与从头计算结果较接近．ＡＭ１和ＰＭ３计算的几何构型较好，但计算的生成热与实验结果偏差较大．ＰＭ３计算值比ＡＭ１的稍好．

利用ABEEM/MM模型对气态丝氨酸和苏氨酸残基二肽分子构象的研究

应用ABEEM/MM浮动电荷模型(原子-键电负性均衡方法融合进分子力场)对气态丝氨酸和苏氨酸残基二肽分子构象进行了初步的研究,与经典的力场模型相比,该方法中的静电势包含了分子内和分子间的静电极化作用,以及分子内电荷转移影响,同时加入了化学键等非原子中心电荷位点,合理的体现了分子中的电荷分布。相对其他极化力场模型,该模型具有计算量较小的特点。结果表明:我们模型计算的两种二肽分子的构象能和关键二面角结构与从头计算结果符合得很好,优于其他力场模型。