Two-state folding and down-hill folding are two kinds of protein folding dynamics for small single domain proteins.Here we apply molecular dynamics(MD)simulation to the two-state protein GB1 and down-hill folding prot...Two-state folding and down-hill folding are two kinds of protein folding dynamics for small single domain proteins.Here we apply molecular dynamics(MD)simulation to the two-state protein GB1 and down-hill folding protein gpW to reveal the relationship of their free energy landscape and folding/unfolding dynamics.Results from the steered MD simulations show that gpW is much less mechanical resistant than GB1,and the unfolding process of gpW has more variability than that of GB1 according to their force-extension curves.The potential of mean force(PMF)of GB1 and gpW obtained by the umbrella sampling simulations shows apparent difference:PMF of GB1 along the coordinate of extension exhibits a kink transition point where the slope of PMF drops suddenly,while PMF of gpW increases with extension smoothly,which are consistent with two-state folding dynamics of GB1 and downhill folding dynamics of gpW,respectively.Our results provide insight to understand the fundamental mechanism of different folding dynamics of twostate proteins and downhill folding proteins.展开更多
We used a combined quantum mechanics and molecular mechanics (QM/MM) method to investigate the solvent effects and potential of mean force of the CH3F+CN- reaction in water. Comparing to gas phase, the water soluti...We used a combined quantum mechanics and molecular mechanics (QM/MM) method to investigate the solvent effects and potential of mean force of the CH3F+CN- reaction in water. Comparing to gas phase, the water solution substantially affects the structures of the stationary points along the reaction path. We quantitatively obtained the solvent effects' contributions to the reaction: 1.7 kcal/mol to the activation barrier and -26.0 kcal/mol to the reaction free energy. The potential mean of force calculated with the density functional theory/MM theory has a barrier height at 19.7 kcal/mol, consistent with the experimental result at 23.0 kcal/mol; the calculated reaction free energy at -43.5 kcal/mol is also consistent with the one estimated based on the gas-phase data at -39.7 kcal/mol.展开更多
The molecular dynamics simulations are performed to show that in aque- ous environments, a short single-walled carbon nanotube (SWCNT) guided by a long SWCNT, either inside or outside the longer tube, is capable of ...The molecular dynamics simulations are performed to show that in aque- ous environments, a short single-walled carbon nanotube (SWCNT) guided by a long SWCNT, either inside or outside the longer tube, is capable of moving along the nanotube axis unidirectionally in an electric field perpendicular to the carbon nanotube (CNT) axis with the linear gradient. The design suggests a new way of molecule transportation or mass delivery. To reveal the mechanism behind this phenomenon, the free energy profiles of the system are calculated by the method of the potential of mean force (PMF).展开更多
Since solid-liquid interfacial nanobubbles(INBs)were first imaged,their long-term stability and large contact angle have been perplexing scientists.This study aimed to investigate the influence of internal gas density...Since solid-liquid interfacial nanobubbles(INBs)were first imaged,their long-term stability and large contact angle have been perplexing scientists.This study aimed to investigate the influence of internal gas density and external gas monolayers on the contact angle and stability of INB using molecular dynamics simulations.First,the contact angle of a water droplet was simulated at different nitrogen densities.The results showed that the contact angle increased sharply with an increase in nitrogen density,which was mainly caused by the decrease in solid-gas interfacial tension.However,when the nitrogen density reached 2.57 nm^(-3),an intervening gas monolayer(GML)was formed between the solid and water.After the formation of GML,the contact angle slightly increased with increasing gas density.The contact angle increased to 180°when the nitrogen density reached 11.38 nm^(-3),indicating that INBs transformed into a gas layer when they were too small.For substrates with different hydrophobicities,the contact angle after the formation of GML was always larger than 140°and it was weakly correlated with substrate hydrophobicity.The increase in contact angle with gas density represents the evolution of contact angle from macro-to nano-bubble,while the formation of GML may correspond to stable INBs.The potential of mean force curves demonstrated that the substrate with GML could attract gas molecules from a longer distance without the existence of a potential barrier compared with the bare substrate,indicating the potential of GML to act as a gas-collecting panel.Further research indicated that GML can function as a channel to transport gas molecules to INBs,which favors stability of INBs.This research may shed new light on the mechanisms underlying abnormal contact angle and long-term stability of INBs.展开更多
This paper reports a classical molecular dynamics study of the potential of mean forces(PMFs),association constants,microstructures K^+-Cl^- ion pair in supercritical fluids.The constrained MD method is used to derive...This paper reports a classical molecular dynamics study of the potential of mean forces(PMFs),association constants,microstructures K^+-Cl^- ion pair in supercritical fluids.The constrained MD method is used to derive the PMFs of K^+-Cl^- ion pair from 673 to 1273 K in low-density water(0.10-0.60 g/cm).The PMF results show that the contact ion-pair(CIP) state is the one most energetically favored for a K^+-Cl^- ion pair.The association constants of the K^+-Cl^- ion pair are calculated from the PMFs,indicating that the K^+-Cl^- ion pair is thermodynamically stable.It gets more stable as T increases or water density decreases.The microstructures of the K^+-Cl^- ion pair in the CIP and solvent-shared ion-pair states are characterized in detail.Moreover,we explore the structures and stabilities of the KCl-Au(I)/Cu(I) complexes by using quantum mechanical calculations.The results reveal that these complexes can remain stable for T up to1273 K,which indicates that KCl may act as a ligand complexing ore-forming metals in hydrothermal fluids.展开更多
The hydrogen mean force from experimental neutron Compton profiles is derived using deep inelastic neutron scattering on amorphous and polycrystalline ice. The formalism of mean force is extended to probe its sensitiv...The hydrogen mean force from experimental neutron Compton profiles is derived using deep inelastic neutron scattering on amorphous and polycrystalline ice. The formalism of mean force is extended to probe its sensitivity to anharmonicity in the hydrogen-nucleus effective potential. The shape of the mean force for amorphous and polycrystalline ice is primarily determined by the anisotropy of the underlying quasi-harmonic effective potential. The data from amorphous ice show an additional curvature reflecting the more pronounced anharmonicity of the effective potential with respect to that of ice Ih.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
Statistical energy functions are general models about atomic or residue-level interactions in biomolecules, derived from existing experimental data. They provide quantitative foundations for structural modeling as wel...Statistical energy functions are general models about atomic or residue-level interactions in biomolecules, derived from existing experimental data. They provide quantitative foundations for structural modeling as well as for structure-based protein sequence design. Statistical energy functions can be derived computationally either based on statistical distributions or based on variational assumptions. We present overviews on the theoretical assumptions underlying the various types of approaches. Theoretical considerations underlying important pragmatic choices are discussed.展开更多
基金Project supported by the National Natural Science Foundation of China(Grant Nos.11874309,11474237,and 11574310)the 111 Project,China(Grant No.B16029).
文摘Two-state folding and down-hill folding are two kinds of protein folding dynamics for small single domain proteins.Here we apply molecular dynamics(MD)simulation to the two-state protein GB1 and down-hill folding protein gpW to reveal the relationship of their free energy landscape and folding/unfolding dynamics.Results from the steered MD simulations show that gpW is much less mechanical resistant than GB1,and the unfolding process of gpW has more variability than that of GB1 according to their force-extension curves.The potential of mean force(PMF)of GB1 and gpW obtained by the umbrella sampling simulations shows apparent difference:PMF of GB1 along the coordinate of extension exhibits a kink transition point where the slope of PMF drops suddenly,while PMF of gpW increases with extension smoothly,which are consistent with two-state folding dynamics of GB1 and downhill folding dynamics of gpW,respectively.Our results provide insight to understand the fundamental mechanism of different folding dynamics of twostate proteins and downhill folding proteins.
基金Project supported by the National Natural Science Foundation of China(Grant No.11774206)Taishan Scholarship Fund from Shandong Province,China
文摘We used a combined quantum mechanics and molecular mechanics (QM/MM) method to investigate the solvent effects and potential of mean force of the CH3F+CN- reaction in water. Comparing to gas phase, the water solution substantially affects the structures of the stationary points along the reaction path. We quantitatively obtained the solvent effects' contributions to the reaction: 1.7 kcal/mol to the activation barrier and -26.0 kcal/mol to the reaction free energy. The potential mean of force calculated with the density functional theory/MM theory has a barrier height at 19.7 kcal/mol, consistent with the experimental result at 23.0 kcal/mol; the calculated reaction free energy at -43.5 kcal/mol is also consistent with the one estimated based on the gas-phase data at -39.7 kcal/mol.
基金Project supported by the National Natural Science Foundation of China(Nos.11372175 and 11272197)the Research Fund for the Doctoral Program of Higher Education of China(No.20103108110004)the Innovation Program of Shanghai Municipality Education Commission(No.14ZZ095)
文摘The molecular dynamics simulations are performed to show that in aque- ous environments, a short single-walled carbon nanotube (SWCNT) guided by a long SWCNT, either inside or outside the longer tube, is capable of moving along the nanotube axis unidirectionally in an electric field perpendicular to the carbon nanotube (CNT) axis with the linear gradient. The design suggests a new way of molecule transportation or mass delivery. To reveal the mechanism behind this phenomenon, the free energy profiles of the system are calculated by the method of the potential of mean force (PMF).
基金This work was supported by the National Natural Science Foundation of China(51920105007,51904300 and 52104277)the Jiangsu Natural Science Fund-Youth Fund(BK20210500).
文摘Since solid-liquid interfacial nanobubbles(INBs)were first imaged,their long-term stability and large contact angle have been perplexing scientists.This study aimed to investigate the influence of internal gas density and external gas monolayers on the contact angle and stability of INB using molecular dynamics simulations.First,the contact angle of a water droplet was simulated at different nitrogen densities.The results showed that the contact angle increased sharply with an increase in nitrogen density,which was mainly caused by the decrease in solid-gas interfacial tension.However,when the nitrogen density reached 2.57 nm^(-3),an intervening gas monolayer(GML)was formed between the solid and water.After the formation of GML,the contact angle slightly increased with increasing gas density.The contact angle increased to 180°when the nitrogen density reached 11.38 nm^(-3),indicating that INBs transformed into a gas layer when they were too small.For substrates with different hydrophobicities,the contact angle after the formation of GML was always larger than 140°and it was weakly correlated with substrate hydrophobicity.The increase in contact angle with gas density represents the evolution of contact angle from macro-to nano-bubble,while the formation of GML may correspond to stable INBs.The potential of mean force curves demonstrated that the substrate with GML could attract gas molecules from a longer distance without the existence of a potential barrier compared with the bare substrate,indicating the potential of GML to act as a gas-collecting panel.Further research indicated that GML can function as a channel to transport gas molecules to INBs,which favors stability of INBs.This research may shed new light on the mechanisms underlying abnormal contact angle and long-term stability of INBs.
基金National Science Foundation of China(Nos.41222015,41273074,41425009,and 41572027)Special Program for Applied Research on Super Computation of the NSFC-Guangdong Joint Fund(the second phase)+1 种基金the Foundation for the Author of National Excellent Doctoral Dissertation of P.R.China (No.201228)Newton International Fellowship Program and the financial support from the State Key Laboratory at Nanjing University
文摘This paper reports a classical molecular dynamics study of the potential of mean forces(PMFs),association constants,microstructures K^+-Cl^- ion pair in supercritical fluids.The constrained MD method is used to derive the PMFs of K^+-Cl^- ion pair from 673 to 1273 K in low-density water(0.10-0.60 g/cm).The PMF results show that the contact ion-pair(CIP) state is the one most energetically favored for a K^+-Cl^- ion pair.The association constants of the K^+-Cl^- ion pair are calculated from the PMFs,indicating that the K^+-Cl^- ion pair is thermodynamically stable.It gets more stable as T increases or water density decreases.The microstructures of the K^+-Cl^- ion pair in the CIP and solvent-shared ion-pair states are characterized in detail.Moreover,we explore the structures and stabilities of the KCl-Au(I)/Cu(I) complexes by using quantum mechanical calculations.The results reveal that these complexes can remain stable for T up to1273 K,which indicates that KCl may act as a ligand complexing ore-forming metals in hydrothermal fluids.
文摘The hydrogen mean force from experimental neutron Compton profiles is derived using deep inelastic neutron scattering on amorphous and polycrystalline ice. The formalism of mean force is extended to probe its sensitivity to anharmonicity in the hydrogen-nucleus effective potential. The shape of the mean force for amorphous and polycrystalline ice is primarily determined by the anisotropy of the underlying quasi-harmonic effective potential. The data from amorphous ice show an additional curvature reflecting the more pronounced anharmonicity of the effective potential with respect to that of ice Ih.
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.
基金This work has been supported by National Natural Science Foundation of China (Grant Nos. 31370755 and 21173203) and the Chinese Ministry of Science and Technology (Grant No. 2012AA02A704).
文摘Statistical energy functions are general models about atomic or residue-level interactions in biomolecules, derived from existing experimental data. They provide quantitative foundations for structural modeling as well as for structure-based protein sequence design. Statistical energy functions can be derived computationally either based on statistical distributions or based on variational assumptions. We present overviews on the theoretical assumptions underlying the various types of approaches. Theoretical considerations underlying important pragmatic choices are discussed.