Molecular Dynamics Simulation To Study The Hydration Of Carboxyammonium Zwitterion

Bioinert is one of the most important essence of biomaterial.Substrate with zwitterionic surface was very capable of antifouling,anti-cell adhesion,immune stealth and had a great outlook in biosensors for specific detection,antibacterial material,tissue engineering,drug encapsulation,bioactivity enhancement,diagnostic imaging and marine science.From studies on mechanism of zwitterionic structure in term of its ultra-bioinert property,hydration was considered as the key factor that still has significant research value today.In this work,molecular dynamics simulations were conducted on two crosslinker molecules in aqueous environment,the zwitterionic carboxybetain dimethacrylate(CBMAX)and the commercially available "hydrophilic" N,N'-methylenebis acrylamide(MBAA),to compare them from different hydration details containing conformational features,structure and dynamics of hydration water,hydrogen bonding,and free energy upon hydration.MD simulations were then performed to characterize the conformational features and hydration dynamics of zwitterionic poly(carboxybetaine methacrylate)(pCBMA).Poly(ethylene glycol)(PEG)with comparable molecular weight was taken as referential counterpart to suggest the differences.The following task was to compare the hydration characters of polymer-grafted surfaces,the pCBMA-g-surface and the PEG-g-surface.Z-density analysis and hydration entropy calculations deriving from the Griding Inhomogeneous Solvation Theory(GIST)were carried out.Umbrella sampling method combined with WHAM was performed to evaluate the adsorption free energy of human serum albumin(HSA)on the two surfaces.Mechanics of bioactivity enhancement upon zwitterion fusion was set as the next research purpose.Native zwitterionic structure like EK peptide consisting of repeat glutamic acid and lysine in sequence functioning to stabilize the secondary structure of three selected target peptides was studied by MD simulations.Contacting map,hydrogen bonding,hydration features as well as the diffusion effect were analyzed.In addition,topology factor without chemical property on surface hydration structure and dynamics was investigated using MD simulations.Artificial surfaces with concave and convex shapes were built,water density and dipole orientation distribution,order parameter for tetrahedral configuration,residence and reorientation dynamics were analyzed and discussed.The main results and findings as followed:1.The CBMAX showed stronger hydration ability,slowing the movements of nearby waters,suppressing the dynamics of H-bond exchanging and making the hydration water more ordered than the MBAA.Conformation analysis revealed the carboxyl pendant group of CBMAX contributed more freedom in term of flexibility,which matters in hydration.2.PEG chain was totally flexible and adopted a curled conformation.Massive segment-to-segment interactions in PEG could result in a hindered hydration effect.While pCBMA had hierarchic flexibility,the fixed backbone and relatively free sidechains,which provided an exclusive hydration volume of each zwitterionic sidechain.In hydration dynamics,pCBMA could largely delay and strongly hydrogen-bond with the surrounding waters.While PEG could suppress the reorientation dynamics of surficial waters due to the enclosed sites and the overlapped hydration volume.Hydration free energy calculations using umbrella sampling revealed the better water affinity of pCBMA against PEG.PEG had high cohesive energy density and needed considerable energy to overcome the barrier upon hydration.3.Basing Z-density analysis,pCBMA-g-surface showed a property of interface with slight flexibility,while the PEG-g-surface had amorphous hydration space,in which one can hardly tell the exact place water molecules rest.The former could largely restrain the movement of hydration waters,the closer to the surface,the higher translational and rotational entropy penalties.As for the latter,the translation entropy cost of hydration water was less related to the surface approaching compared to the former,and the rotation entropy was totally unrelated to the surface.Both surfaces expressed the ability to resist the protein adsorption,but their mechanisms were different:pCBMA-g-surface forms a stable hydration layer through electrostatic interactions,that builds up large energy barrier to prevent the protein molecule approaching;PEG chain on the grafted surface can be much flexible and move randomly in all directions with thermal motions of water,thus produces excluded volume effect to resist protein adsorption.4.Compared with bulk water,the EK chain could stabilize the secondary structure of target peptides.The lower coordinates number of hydration with EK made the nearby environment of peptide "dryer" than in bulk.EK solution could largely conserve the intramolecular hydrogen bonding which directly strengthens the secondary structure of peptides.From MSD and coefficient of diffusion calculations,we found that water in EK solution(0.03mol/L)at 300K had a comparable diffusion ability with bulk at 297K,meaning the EK carried "cooling" effect on the aqueous environment of peptides.5.At water-surface(concave or convex)interface,water could generate discernible 2?3 layers,the density fluctuation range was about lnm.That is because the Van der Waals potential exerts on the O atoms and the H atoms resulting in different effects.Surface with concave shape impacted the water diplo orientation distribution,the regularity of tetrahedral configuration as well as the dynamics of residence and reorientation a bit more than that with convex sharp.Temperature could significantly influence the tetrahedral regularity but not the pattern of diplo orientation distribution nor the structure of water layer.