| Metals and metal ions are ubiquitous in nature and have a large chemical diversity.Because metals have low electronegativity,can be easily ionized and have high reactivity,they can participate in many chemical reactions and catalytic processes.Metals and metal ions play an important role in the fields of chemistry,geochemistry,biochemistry,and materials science.About one-third of the structures in the Protein Data Bank(PDB)contain metal ions.Molecular containers in supramolecular chemistry include a variety of nano-supramolecules formed by the coordination of metal ions.However,in resent force field simulation protocols,there are still many problems in the parameterization of metal ions.This drawback severely restricts the theoretical investigation on the biological processes dominated by protein-cofactor interactions and the supramolecular chemistry drived by metal coordination.In this dissertation,we used theories and methods in mathematics,computer science,and bioinformatics to study the following questions:(1)How to describe the interaction among metal ions,cofactors and proteins more accurately using the classical force field;(2)How to correctly describe the self-assembly and guest encapsulation behavior of coordination-directed self-assembly nanocapsules.The work of this dissertation provides new methods and knowledge for the theoretical study(modeling and simulation)of supramolecular chemistry.The main work of the dissertation is as follows:1.Refinement of the Cationic Dummy Atom(CaDA)Model Parameters for Mg2+.We provided a simple algorithm for refining the van der Waals potential function parameters of the CaDA model,and successfully refined the previous Mg2+ CaDA model parameters using this algorithm.We used a more accurate proton hydration free energy to correct the experimental values of Mg2+hydration free energy.In the hydration free energy calculation,the corrections for the errors induced by using the PME method and omitting the vacuum-water interface were added to ensure the accuracy of the hydration free energy calculation.The refined Mg2+ CaDA model can accurately reproduce the experimental metal-oxygen distance,coordination number and hydration free energy of Mg2+ at the same time.The parameter refining protocol can be applied to re-optimize the same metal ion model in different force fields(different potential function expressions and calculation rules)and expand the application scope of the metal ion model.2.Force Field Parameter Development of CaDA Models for Divalent Six-coordinated Metal Ions.Based on the parameter refining protocol,we further provided a force field parameter development method.This method aims to reproduce the hydration free energy,metal-oxygen distance and coordination number of metal ions.The development of new parameters is accomplished through the scan of parameter space,reconstruction of the free energy surface and the metal-oxygen distance surface and projection of experimental values.The CaDA models of eleven divalent six-coordinated metal ions(Mg2+,V2+,Cr2+,Mn2+,Fe2+,Co2+,Ni2+,Zn2+,Cd2+,Sn2+ and Hg2+)developed through this method can accurately reproduce the experimental ionic hydration free energy,coordination distance and coordination number at the same time.The simulation performance of the new models is greatly improved compared with that of the previous models.3.Comprehensive Test of New Models.We performed a comprehensive test of the simulation performance of the newly developed CaDA model in biomolecular systems.In terms of the prediction performance of the water exchange rate constant,all models that are not developed to reproduce this quantity predicted incorrect values:the CaDA model underestimates this quantity,while the point charge model overestimates it.In the binuclear metal-cofactor systems,the CaDA model developed in this work has high simulation performance,and can accurately reproduce the corresponding coordination structure to an extent close to the covalent model.What is important is that this model can produce a more reasonable hydrogen bond network for cofactors.However,the binuclear metal distance and the coordination mode of the carboxyl side chain cannot be reproduced well.In the mononuclear metal-cofactor system,all the tested models yielded good results.In the metal substitution system,the CaDA model developed in this work has the best simulation performance.However,limited by the theoretical level of the model itself,the six-coordinated model cannot produce non-six-coordinated structures.Overall,the newly developed CaDA model has superior simulation performance.To a certain extent,the classical force field with this new CaDA model can accurately describe the interaction of metal,cofactors and proteins.4.Study of Self-assembly Behavior and Supramolecular Structure Conversion of Coordination-directed Self-assembly Nanocapsule M2L4.We used the CaDA model and implicit solvent model coupled with simulated annealing method to simulate the self-assembly of the nanocapsule.From the molecular dynamics(MD)simulation,we concluded that the self-assembly process of M2L4 nanocapsule follows the principle of minimum potential energy.It is a spontaneous process:from disorder to order and from high potential energy to low potential energy.There are many intermediates and semi-stable states during the self-assembly process.It also showed a stepwise self-assembly behavior:gradually self-assembled from M2L2 metallacycle to M2L3 nanocage and then to M2L4 nanocapsule.There are dynamic supramolecular structure conversions in the self-assembly process.The transient increase of local ligand concentration will promote the conversion of M2L2 metallacycles into M2L4 nanocapsules.When M2L4 nanocapsules are formed in the system,the transient increase of local metal ion concentration will also promote the conversion of M2L4 nanocapsules back into M2L2 metallacycles.M2L3 nanocages act as a transition structure.When the concentration of available metal ions is reduced to a certain extent,M2L4 nanocapsules and M2L3 nanocages are difficult to be converted back into M2L2 metallacycles,and stable M2L4 nanocapsules are finally formed.5.Study of Guest Encapsulation Behavior of Coordination-directed Self-assembly Nanocapsule M2L4.We used the MD simulation to investigate the guest encapsulation behavior during the dynamic self-assembly process(supramolecular structure conversion),and successfully reproduce the competitive encapsulation of two fullerene guests.Finally,the fullerene guests selectivities of different supramolecular structures that were observed in the dynamic self-assembly process were successfully predicted,which is in complete agreement with the experimental observations.We concluded that the driving force of fullerene guest encapsulation arises from ?-? stacking.This process follows the principle of minimum potential energy.The encapsulation ability and selectivity for fullerene guests are highly dependent on the shape and volume of the guest molecules,as well as the supramolecular structures.M2L4 and M2L3 nanocapsules(nanocages)showed high selectivities to spherical and small fullerene C60,while M2L2 metalacycles showed a slightly higher selectivity to ellipsoidal and larger fullerene C70.During the dynamic structural changes that respond to the surrounding environment,fullerene guests released due to the weakened ?-? stacking interactions and encapsulation capabilities that caused by the open structure of the M2L2 metallacycle. |
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