Objective In this study,we aimed to assess the characteristics of the P3 component from an event-related potential(ERP)that was induced by visual acuity(VA)processing.Furthermore,we sought to provide electrophysiologi...Objective In this study,we aimed to assess the characteristics of the P3 component from an event-related potential(ERP)that was induced by visual acuity(VA)processing.Furthermore,we sought to provide electrophysiological evidence for the objective evaluation of VA.Methods We recruited 32 participants with myopia-related ametropia.They reported no other ocular diseases and had an uncorrected VA of 4.0 in both eyes.We used the block letter“E”at different visual angles and orientations as the graphic stimuli.The oddball paradigm,consisting of 4 modules,was used for ERP analysis.The standard stimuli of each module were identical,with a visual angle of 1°15′.The visual angles of the target stimuli were 1°15′,55′,24′,and 15′.The VA test was performed on each eye separately for all participants,and all characteristics of the P3 component were analyzed.Results There was no significant difference in the P3 peak letencies between the target stimulation angle 1°15′group and the 55′group,or between the target stimulation angle 24′group and the 15′group.There was a significant difference in the P3 peak letencies between the target stimulation angle 1°15′group and the 24′group as well as the 15′group.There was a significant difference in the P3 peak letencies between the target stimulation angle 55′group and the 24′group as well as the 15′group.No significant differences were observed in the P3 amplitude between modules.Conclusion In the oddball paradigm,P3 elicitation indicated a cognitive response to the target stimuli.These data showed that the characteristics of P3 can be used as an objective evaluation of VA.展开更多
This paper applies the density functional theory method to optimise the structure for X3A state of TiO molecule with the basis sets 6-31G, 6-31++G and 6-311G^**. Comparing the attained results with the experiments...This paper applies the density functional theory method to optimise the structure for X3A state of TiO molecule with the basis sets 6-31G, 6-31++G and 6-311G^**. Comparing the attained results with the experiments, it obtains the conclusion that the basis set 6-31++G is most suitable for the optimal structure calculations of X3A state of TiO molecule. The whole potential energy curve for the electronic state is further scanned by using B3P86/6-31++G method for the ground state, then it uses a least square fitted to Murrell-Sorbie functions, at last it calculates the spectroscopic constants and force constants, which are in better agreement with the experimental data.展开更多
This study investigated behavioral inhibition in female college students with psychometrically defined schizotypal traits using a Go/NoGo task and event-related potentials (ERPs). The schizotypal-trait (n = 15) and no...This study investigated behavioral inhibition in female college students with psychometrically defined schizotypal traits using a Go/NoGo task and event-related potentials (ERPs). The schizotypal-trait (n = 15) and normal control (n = 15) groups were selected based on scores of the Schizotypal Personality Questionnaire (SPQ). The Go/NoGo task consisted of Go (requires response) and NoGo (requires no response) conditions. In terms of response time and accuracy rate for the Go/NoGo task, the two groups did not differ significantly. In terms of ERPs, the control group showed greater N2 amplitudes in response to NoGo (NoGo-N2) than to Go stimuli (Go-N2), whereas the schizotypal-trait group showed no significant difference in NoGo-N2 and Go-N2 amplitudes. In addition, the schizotypal-trait group showed reduced NoGo-N2 amplitudes at the frontal site compared to controls, and an association between SPQ scores and NoGo-N2 amplitudes measured at the frontal site. The two groups did not differ in P3 amplitudes. Since the N2 reflects the detection of response conflict and behavioral inhibition, the present results indicate that nonclinical individuals with schizotypal traits have difficulties in detecting response conflict and behavioral inhibition.展开更多
Objective: To investigate the effect of acupuncture ("JIN’s San Zhen") on infantile mental retardation (MR). Methods: 44 cases of MR children were attributed to treatment group and 39 normal children to con...Objective: To investigate the effect of acupuncture ("JIN’s San Zhen") on infantile mental retardation (MR). Methods: 44 cases of MR children were attributed to treatment group and 39 normal children to control group. P 3 (event related potential) and brainstem evoked potentials were used as the indexes. Acupoints "Si shen Zhen", "Head Zhi San Zhen", "Hand Zhi San Zhen", "Foot Zhi San Zhen" were punctured with filiform needles, and stimulated by manipulating the needle once every 5 minutes with uniform reinforcing reducing method. The treatment was conducted once daily, 6 times every week, with 4 months being a therapeutic course. Results: In comparison with normal children, the latency of P 3 was longer and its amplitude lower in MR children. After 4 months’ acupuncture treatment, the latency was shortened and the amplitude increased significantly in comparison with pre treatment (P<0.01, 0.05). Results of the total intelligence quotient (TIQ) evaluation showed a 70.3% coincidence rate compared with improvement of P 3. Conclusion: Changes of P 3 and BAEP(brain auditory evoked potential) after acupuncture treatment may be related to the effect of "JIN’s San Zhen" in bettering clinical symptoms and signs of MR infantile patients.展开更多
In this study, we report the influences of oxidation potential and holding time on the electrochromic(EC) stability of poly(3-methylthiophene)(P3MT) film during the electrochemical reaction. The cycle stability and tr...In this study, we report the influences of oxidation potential and holding time on the electrochromic(EC) stability of poly(3-methylthiophene)(P3MT) film during the electrochemical reaction. The cycle stability and transmittance changes of the film were investigated by optimizing the oxidation potential, and its chemical compositions were measured by x-ray photoelectron spectra after multiple electrochemical cycles. High oxidation potentials can increase the P3MT film color contrast and decrease its cycle stability because of accelerating chemical decomposition. Moreover, the holding time with potential pulsing was analyzed by using the optical memory of P3MT at an optimized oxidation potential, which revealed the reduced voltage duration saved energy consumption by 11.6% and improved the EC cycle stability without changing in color contrast.展开更多
目的对2021年采集于我国福建的A组轮状病毒(group A rotavirus,RVA)G3P[8]毒株FJ21351116进行全基因组分子特征分析。方法使用高灵敏度A组轮状病毒全基因组测序方法对FJ21351116进行全基因组测序。用MEGA11.0、Geneious9.0.2和DNASTAR...目的对2021年采集于我国福建的A组轮状病毒(group A rotavirus,RVA)G3P[8]毒株FJ21351116进行全基因组分子特征分析。方法使用高灵敏度A组轮状病毒全基因组测序方法对FJ21351116进行全基因组测序。用MEGA11.0、Geneious9.0.2和DNASTAR软件通过核酸序列分析评估病毒的基因组特征。使用BioEdit v.7.0.9.0和PyMOL v.2.5.2分析VP7和VP4(VP8*)的中和表位。结果我国福建RVA毒株FJ21351116基因型为G3-P[8]-I2-R2-C2-M2-A2-N2-T2-E2-H2,系统进化分析显示,FJ21351116株的VP7、VP4、VP3、NSP2-NSP5基因与近几年日本检测到的马样DS-1样G3P[8]基因存在亲缘关系。而VP6、VP1、VP2、NSP1基因与大部分国家G2P[4]的相应基因亲缘关系近,特别是新加坡,表明该毒株是马样G3P[8]毒株与G2P[4]毒株共感染过程中通过基因重配形成的。FJ21351116的VP7/VP4基因与Rotarix和RotaTeq疫苗的进化分析表明,VP7和VP4(VP8*)中和抗原表位与疫苗氨基酸位点均存在多个突变。推测Rotarix和RotaTeq疫苗针对马样DS-1样G3P[8]RVA的保护效果不佳,且与Rotarix的中和抗原表位氨基酸差异高于RotaTeq。结论本研究发现一例中国罕见的DS-1样G3P[8]型RVA毒株,且疫苗株可能对其保护效果差,强调了持续监测RVA毒株及研发高效覆盖面全的RVA疫苗的重要性。展开更多
Alzheimer ’s disease(AD) is a leading cause of dementia in the elderly.Mitogen-activated protein kinase phosphatase 1(MKP-1) plays a neuroprotective role in AD.However,the molecular mechanisms underlying the effects ...Alzheimer ’s disease(AD) is a leading cause of dementia in the elderly.Mitogen-activated protein kinase phosphatase 1(MKP-1) plays a neuroprotective role in AD.However,the molecular mechanisms underlying the effects of MKP-1 on AD have not been extensively studied.MicroRNAs(miRNAs) regulate gene expression at the post-transcriptional level,thereby repressing mRNA translation.Here,we reported that the microRNA-429-3p(miR-429-3p) was significantly increased in the brain of APP23/PS45 AD model mice and N2AAPPAD model cells.We further found that miR-429-3p could downregulate MKP-1 expression by directly binding to its 3’-untranslated region(3’ UTR).Inhibition of miR-429-3p by its antagomir(A-miR-429) restored the expression of MKP-1 to a control level and consequently reduced the amyloidogenic processing of APP and Aβ accumulation.More importantly,intranasal administration of A-miR-429 successfully ameliorated the deficits of hippocampal CA1 long-term potentiation and spatial learning and memory in AD model mice by suppressing extracellular signal-regulated kinase(ERK1/2)-mediated GluAl hyperphosphorylation at Ser831 site,thereby increasing the surface expression of GluAl-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors(AMPARs).Together,these results demonstrate that inhibiting miR-429-3p to upregulate MKP-1 effectively improves cognitive and synaptic functions in AD model mice,suggesting that miR-429/MKP-1 pathway may be a novel therapeutic target for AD treatment.展开更多
In peripheral artery disease patients,the blood supply directed to the lower limbs is reduced.This results in severe limb ischemia and thereby enhances pain sensitivity in lower limbs.The painful perception is induced...In peripheral artery disease patients,the blood supply directed to the lower limbs is reduced.This results in severe limb ischemia and thereby enhances pain sensitivity in lower limbs.The painful perception is induced and exaggerate during walking,and is relieved by rest.This symptom is termed by intermittent claudication.The limb ischemia also amplifies autonomic responses during exercise.In the process of pain and autonomic responses originating exercising muscle,a number of receptors in afferent nerves sense ischemic changes and send signals to the central nervous system leading to autonomic responses.This review integrates recent study results in terms of perspectives including how nerve growth factor affects muscle sensory nerve receptors in peripheral artery disease and thereby alters responses of sympathetic nerve activity and blood pressure to active muscle.For the sensory nerve receptors,we emphasize the role played by transient receptor potential vanilloid type 1,purinergic P2X purinoceptor 3 and acid sensing ion channel subtype 3 in amplified sympathetic nerve activity responses in peripheral artery disease.展开更多
The main aim of the present paper is to establish an intrinsic investigation of the energy β-conformal change of the most important special Finsler spaces, namely, Ch-recurrent, Cv-recurrent, C0-recurrent, Sv-recurre...The main aim of the present paper is to establish an intrinsic investigation of the energy β-conformal change of the most important special Finsler spaces, namely, Ch-recurrent, Cv-recurrent, C0-recurrent, Sv-recurrent, quasi-C-reducible, semi-C-reducible, C-reducible, P-reducible, C2-like, S3-like, P2-like and h-isotropic, ···, etc. Necessary and sufficient conditions for such special Finsler manifolds to be invariant under an energy β-conformal change are obtained. It should be pointed out that the present work is formulated in a prospective modern coordinate-free form.展开更多
The reaction of O(<sup>3</sup>P) with CH<sub>2</sub>Cl radical has been studied using ab initio molecular orbital theory. G2 (MP2) method is used to calculate the geometrical parameters, vi...The reaction of O(<sup>3</sup>P) with CH<sub>2</sub>Cl radical has been studied using ab initio molecular orbital theory. G2 (MP2) method is used to calculate the geometrical parameters, vibrational frequencies and energies of various stationary points on the potential energy surface. The reaction mechanism is revealed. The addition of O(<sup>3</sup>P) with CH<sub>2</sub>Cl leads to the formation of an energy rich intermediate OCH<sub>2</sub>Cl which can subsequently undergo decomposition or isomerization to the final products. The calculated heat of reaction for each channel is in agreement with the experimental value. The production of H+CHClO and Cl+CH<sub>2</sub>O are predicted to be the major channels. The overall rate constants are calculated using transition state theory on the basis of ab initio data. The rate constant is pressure independent and exhibits negative temperature dependence at lower temperatures, in accordance with the experimental results.展开更多
Recently,it was demonstrated that implicit solvent models were capable of generating stable B-form DNA structures.Specifically,generalized Born(GB)implicit solvent models have improved regarding the solvation of confo...Recently,it was demonstrated that implicit solvent models were capable of generating stable B-form DNA structures.Specifically,generalized Born(GB)implicit solvent models have improved regarding the solvation of conformational sampling of DNA[1,2].Here,we examine the performance of the GBSW and GBMV models in CHARMM for characterizing base flipping free energy profiles of undamaged and damaged DNA bases.Umbrella sampling of the base flipping process was performed for the bases cytosine,uracil and xanthine.The umbrella sampling simulations were carried-out with both explicit(TIP3P)and implicit(GB)solvent in order to establish the impact of the solvent model on base flipping.Overall,base flipping potential of mean force(PMF)profiles generated with GB solvent resulted in a greater free energy difference of flipping than profiles generated with TIP3P.One of the significant differences between implicit and explicit solvent models is the approximation of solute-solvent interactions in implicit solvent models.We calculated electrostatic interaction energies between explicit water molecules and the base targeted for flipping.These interaction energies were calculated over the base flipping reaction coordinate to illustrate the stabilizing effect of the explicit water molecules on the flipped-out state.It is known that nucleic base pair hydrogen bonds also influenced the free energy of flipping since these favorable interactions must be broken in order for a base to flip-out of the helix.The Watson-Crick base pair hydrogen bond fractions were calculated over the umbrella sampling simulation windows in order to determine the effect of base pair interactions on the base flipping free energy.It is shown that interaction energies between the flipping base and explicit water molecules are responsible for the lower base flipping free energy difference in the explicit solvent PMF profiles.展开更多
基金This project was supported by the National Key Research and Development Program of China during the Thirteenth Five-Year Plan period(No.2016YFC0800701-4-2).
文摘Objective In this study,we aimed to assess the characteristics of the P3 component from an event-related potential(ERP)that was induced by visual acuity(VA)processing.Furthermore,we sought to provide electrophysiological evidence for the objective evaluation of VA.Methods We recruited 32 participants with myopia-related ametropia.They reported no other ocular diseases and had an uncorrected VA of 4.0 in both eyes.We used the block letter“E”at different visual angles and orientations as the graphic stimuli.The oddball paradigm,consisting of 4 modules,was used for ERP analysis.The standard stimuli of each module were identical,with a visual angle of 1°15′.The visual angles of the target stimuli were 1°15′,55′,24′,and 15′.The VA test was performed on each eye separately for all participants,and all characteristics of the P3 component were analyzed.Results There was no significant difference in the P3 peak letencies between the target stimulation angle 1°15′group and the 55′group,or between the target stimulation angle 24′group and the 15′group.There was a significant difference in the P3 peak letencies between the target stimulation angle 1°15′group and the 24′group as well as the 15′group.There was a significant difference in the P3 peak letencies between the target stimulation angle 55′group and the 24′group as well as the 15′group.No significant differences were observed in the P3 amplitude between modules.Conclusion In the oddball paradigm,P3 elicitation indicated a cognitive response to the target stimuli.These data showed that the characteristics of P3 can be used as an objective evaluation of VA.
基金supported by the Basic Research Program of Education Bureau of Henan Province,China (Grant No.2010A140008)the National Natural Science Foundation of China (Grant No.10774039)the Natural Science Foundation of Henan Province,China (Grant No.092300410249)
文摘This paper applies the density functional theory method to optimise the structure for X3A state of TiO molecule with the basis sets 6-31G, 6-31++G and 6-311G^**. Comparing the attained results with the experiments, it obtains the conclusion that the basis set 6-31++G is most suitable for the optimal structure calculations of X3A state of TiO molecule. The whole potential energy curve for the electronic state is further scanned by using B3P86/6-31++G method for the ground state, then it uses a least square fitted to Murrell-Sorbie functions, at last it calculates the spectroscopic constants and force constants, which are in better agreement with the experimental data.
文摘This study investigated behavioral inhibition in female college students with psychometrically defined schizotypal traits using a Go/NoGo task and event-related potentials (ERPs). The schizotypal-trait (n = 15) and normal control (n = 15) groups were selected based on scores of the Schizotypal Personality Questionnaire (SPQ). The Go/NoGo task consisted of Go (requires response) and NoGo (requires no response) conditions. In terms of response time and accuracy rate for the Go/NoGo task, the two groups did not differ significantly. In terms of ERPs, the control group showed greater N2 amplitudes in response to NoGo (NoGo-N2) than to Go stimuli (Go-N2), whereas the schizotypal-trait group showed no significant difference in NoGo-N2 and Go-N2 amplitudes. In addition, the schizotypal-trait group showed reduced NoGo-N2 amplitudes at the frontal site compared to controls, and an association between SPQ scores and NoGo-N2 amplitudes measured at the frontal site. The two groups did not differ in P3 amplitudes. Since the N2 reflects the detection of response conflict and behavioral inhibition, the present results indicate that nonclinical individuals with schizotypal traits have difficulties in detecting response conflict and behavioral inhibition.
文摘Objective: To investigate the effect of acupuncture ("JIN’s San Zhen") on infantile mental retardation (MR). Methods: 44 cases of MR children were attributed to treatment group and 39 normal children to control group. P 3 (event related potential) and brainstem evoked potentials were used as the indexes. Acupoints "Si shen Zhen", "Head Zhi San Zhen", "Hand Zhi San Zhen", "Foot Zhi San Zhen" were punctured with filiform needles, and stimulated by manipulating the needle once every 5 minutes with uniform reinforcing reducing method. The treatment was conducted once daily, 6 times every week, with 4 months being a therapeutic course. Results: In comparison with normal children, the latency of P 3 was longer and its amplitude lower in MR children. After 4 months’ acupuncture treatment, the latency was shortened and the amplitude increased significantly in comparison with pre treatment (P<0.01, 0.05). Results of the total intelligence quotient (TIQ) evaluation showed a 70.3% coincidence rate compared with improvement of P 3. Conclusion: Changes of P 3 and BAEP(brain auditory evoked potential) after acupuncture treatment may be related to the effect of "JIN’s San Zhen" in bettering clinical symptoms and signs of MR infantile patients.
基金Project supported by the National Natural Science Foundation of China(Grant No.51403102)the Natural Science Foundation of Jiangsu Province,China(Grant No.BK20140811)
文摘In this study, we report the influences of oxidation potential and holding time on the electrochromic(EC) stability of poly(3-methylthiophene)(P3MT) film during the electrochemical reaction. The cycle stability and transmittance changes of the film were investigated by optimizing the oxidation potential, and its chemical compositions were measured by x-ray photoelectron spectra after multiple electrochemical cycles. High oxidation potentials can increase the P3MT film color contrast and decrease its cycle stability because of accelerating chemical decomposition. Moreover, the holding time with potential pulsing was analyzed by using the optical memory of P3MT at an optimized oxidation potential, which revealed the reduced voltage duration saved energy consumption by 11.6% and improved the EC cycle stability without changing in color contrast.
文摘目的对2021年采集于我国福建的A组轮状病毒(group A rotavirus,RVA)G3P[8]毒株FJ21351116进行全基因组分子特征分析。方法使用高灵敏度A组轮状病毒全基因组测序方法对FJ21351116进行全基因组测序。用MEGA11.0、Geneious9.0.2和DNASTAR软件通过核酸序列分析评估病毒的基因组特征。使用BioEdit v.7.0.9.0和PyMOL v.2.5.2分析VP7和VP4(VP8*)的中和表位。结果我国福建RVA毒株FJ21351116基因型为G3-P[8]-I2-R2-C2-M2-A2-N2-T2-E2-H2,系统进化分析显示,FJ21351116株的VP7、VP4、VP3、NSP2-NSP5基因与近几年日本检测到的马样DS-1样G3P[8]基因存在亲缘关系。而VP6、VP1、VP2、NSP1基因与大部分国家G2P[4]的相应基因亲缘关系近,特别是新加坡,表明该毒株是马样G3P[8]毒株与G2P[4]毒株共感染过程中通过基因重配形成的。FJ21351116的VP7/VP4基因与Rotarix和RotaTeq疫苗的进化分析表明,VP7和VP4(VP8*)中和抗原表位与疫苗氨基酸位点均存在多个突变。推测Rotarix和RotaTeq疫苗针对马样DS-1样G3P[8]RVA的保护效果不佳,且与Rotarix的中和抗原表位氨基酸差异高于RotaTeq。结论本研究发现一例中国罕见的DS-1样G3P[8]型RVA毒株,且疫苗株可能对其保护效果差,强调了持续监测RVA毒株及研发高效覆盖面全的RVA疫苗的重要性。
基金supported by grants from the National Natural Science Foundation of China (32371030, 82371194, 82071395 and 82001158)the Natural Science Foundation of Chongqing(CSTB2022NSCQ-LZX0010 and cstc2021ycjh-bgzxm0186, China)+1 种基金the Scientific and Technological Innovation Project for the Construction of Chengdu-Chongqing Economic Circle (KJCX ZD2020021, China)CQMU Program for Youth Innovation in Future Medicine (W0044, China)
文摘Alzheimer ’s disease(AD) is a leading cause of dementia in the elderly.Mitogen-activated protein kinase phosphatase 1(MKP-1) plays a neuroprotective role in AD.However,the molecular mechanisms underlying the effects of MKP-1 on AD have not been extensively studied.MicroRNAs(miRNAs) regulate gene expression at the post-transcriptional level,thereby repressing mRNA translation.Here,we reported that the microRNA-429-3p(miR-429-3p) was significantly increased in the brain of APP23/PS45 AD model mice and N2AAPPAD model cells.We further found that miR-429-3p could downregulate MKP-1 expression by directly binding to its 3’-untranslated region(3’ UTR).Inhibition of miR-429-3p by its antagomir(A-miR-429) restored the expression of MKP-1 to a control level and consequently reduced the amyloidogenic processing of APP and Aβ accumulation.More importantly,intranasal administration of A-miR-429 successfully ameliorated the deficits of hippocampal CA1 long-term potentiation and spatial learning and memory in AD model mice by suppressing extracellular signal-regulated kinase(ERK1/2)-mediated GluAl hyperphosphorylation at Ser831 site,thereby increasing the surface expression of GluAl-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors(AMPARs).Together,these results demonstrate that inhibiting miR-429-3p to upregulate MKP-1 effectively improves cognitive and synaptic functions in AD model mice,suggesting that miR-429/MKP-1 pathway may be a novel therapeutic target for AD treatment.
基金This work was supported by the National Institutes of Health,No.NIH P01 HL134609 and R01 HL141198(to JL).
文摘In peripheral artery disease patients,the blood supply directed to the lower limbs is reduced.This results in severe limb ischemia and thereby enhances pain sensitivity in lower limbs.The painful perception is induced and exaggerate during walking,and is relieved by rest.This symptom is termed by intermittent claudication.The limb ischemia also amplifies autonomic responses during exercise.In the process of pain and autonomic responses originating exercising muscle,a number of receptors in afferent nerves sense ischemic changes and send signals to the central nervous system leading to autonomic responses.This review integrates recent study results in terms of perspectives including how nerve growth factor affects muscle sensory nerve receptors in peripheral artery disease and thereby alters responses of sympathetic nerve activity and blood pressure to active muscle.For the sensory nerve receptors,we emphasize the role played by transient receptor potential vanilloid type 1,purinergic P2X purinoceptor 3 and acid sensing ion channel subtype 3 in amplified sympathetic nerve activity responses in peripheral artery disease.
文摘The main aim of the present paper is to establish an intrinsic investigation of the energy β-conformal change of the most important special Finsler spaces, namely, Ch-recurrent, Cv-recurrent, C0-recurrent, Sv-recurrent, quasi-C-reducible, semi-C-reducible, C-reducible, P-reducible, C2-like, S3-like, P2-like and h-isotropic, ···, etc. Necessary and sufficient conditions for such special Finsler manifolds to be invariant under an energy β-conformal change are obtained. It should be pointed out that the present work is formulated in a prospective modern coordinate-free form.
文摘The reaction of O(<sup>3</sup>P) with CH<sub>2</sub>Cl radical has been studied using ab initio molecular orbital theory. G2 (MP2) method is used to calculate the geometrical parameters, vibrational frequencies and energies of various stationary points on the potential energy surface. The reaction mechanism is revealed. The addition of O(<sup>3</sup>P) with CH<sub>2</sub>Cl leads to the formation of an energy rich intermediate OCH<sub>2</sub>Cl which can subsequently undergo decomposition or isomerization to the final products. The calculated heat of reaction for each channel is in agreement with the experimental value. The production of H+CHClO and Cl+CH<sub>2</sub>O are predicted to be the major channels. The overall rate constants are calculated using transition state theory on the basis of ab initio data. The rate constant is pressure independent and exhibits negative temperature dependence at lower temperatures, in accordance with the experimental results.
基金supported by National Science Foundation Career Award MCB-0953783(to B.N.D.).
文摘Recently,it was demonstrated that implicit solvent models were capable of generating stable B-form DNA structures.Specifically,generalized Born(GB)implicit solvent models have improved regarding the solvation of conformational sampling of DNA[1,2].Here,we examine the performance of the GBSW and GBMV models in CHARMM for characterizing base flipping free energy profiles of undamaged and damaged DNA bases.Umbrella sampling of the base flipping process was performed for the bases cytosine,uracil and xanthine.The umbrella sampling simulations were carried-out with both explicit(TIP3P)and implicit(GB)solvent in order to establish the impact of the solvent model on base flipping.Overall,base flipping potential of mean force(PMF)profiles generated with GB solvent resulted in a greater free energy difference of flipping than profiles generated with TIP3P.One of the significant differences between implicit and explicit solvent models is the approximation of solute-solvent interactions in implicit solvent models.We calculated electrostatic interaction energies between explicit water molecules and the base targeted for flipping.These interaction energies were calculated over the base flipping reaction coordinate to illustrate the stabilizing effect of the explicit water molecules on the flipped-out state.It is known that nucleic base pair hydrogen bonds also influenced the free energy of flipping since these favorable interactions must be broken in order for a base to flip-out of the helix.The Watson-Crick base pair hydrogen bond fractions were calculated over the umbrella sampling simulation windows in order to determine the effect of base pair interactions on the base flipping free energy.It is shown that interaction energies between the flipping base and explicit water molecules are responsible for the lower base flipping free energy difference in the explicit solvent PMF profiles.