The Mechanisms Of The Interactions Between Protein And Several Polar Nanomaterials:A Molecular Dynamics Simulation Study

In recent years,polar nanomaterials(NMs)have gained significant attention due to their applications in the field of biomedicine.These NMs inevitably interact with proteins during their utilization.However,the molecular mechanisms underlying their interactions and the possible subsequent biological effects remain poorly understood.Hence,three typical systems of protein-NM were chosen for all-atom MD simulations to investigate the molecular mechanisms of their interactions,and then to comprehensively analyse the impacts and mechanisms of surface polarity of NM,temperature(high temperature)and persulfidation of protein induced by redox signaling on their interactions.The details are shown as follows:(1)We investigated the interactions between complement protein g C1 q from immune system and two typical NMs,and further studied the effects of surface polarities of NMs on the binding behavior of g C1 q.The results show that the gh C module of g C1 q tends to bind to NM with weak surface polarity,while the gh B module tends to bind to NM with strong surface polarity.The distinct binding modes are mainly ascribed to different surface polarities of the binding modules(gh B,gh C)of g C1 q which produces the preferential binding of g C1q(gh B)with NM with strong surface polarity driven via hydrogen bond and electrostatic interaction.It also makes g C1q(gh C)form favorable hydrophobic and van der Waals interaction and then bind with NM with weak surface polarity.Taken together,this study provides theoretical insights into the improvement of the biocompatibility of NM by adjusting its surface polarity and subsequent immune response.(2)We investigated the non-specific binding behavior of human serum albuim(HSA)from polar self-assembled monolayer(SAM)coated gold nanoparticle and the impacts of high temperature.When the temperature increases from 300 K to 350 K,the binding stability of HSA reduces and eventually prompts its desorption from SAM.However,when the temperature further increases to 400 K,HSA re-adsorbes on SAM.HSA adsorbes on the surface of SAM due to salt bridges formed between HSA and SAM at 300 K.These salt bridges diminish considerably due to the enhanced lateral diffusion of HSA on the SAM at the temperature of 350 K,which makes the interaction contributed by salt briges weaker than interfacial hydration,and consequently makes protein detach from SAM.When the temperature further increases to 400 K,HSA shows a large increase in structural flexibility,thus contributing to more exposure of negatively charged residues,and more salt bridges formed between HSA and SAM.Consequently,it makes the interaction contributed by salt briges stronger than interfacial hydration,thereby prompting its re-adsorption on SAM.Taken together,this study improves the understanding of the mechanism of nonspecific binding of protein on polar NM and also provides new insights into the controlled release of protein drug from nanocarriers under the regulation of high temperature.(3)The binding of HNF1α with DNA nanostructure and the impacts of persulfidation of HNF1α induced by redox signaling were investigated.HNF1α can bind DNA via hydrogen bonds and salt bridges.After the persulfidation of HNF1α,its binding stability attenuates.The elaborated hydrogen bond network formed between persulfidated cysteine and surrounding residues causes the structural change of protein and further induces orientational adjustment and positional change of the interfacial residues of HNF1αresponsible for binding with DNA.As a result,the hydrogen bonds and salt bridges formed between HNF1α and DNA diminish thereby reducing their binding stability.Taken together,the results of this study are helpful in understanding the mechanism of response of proteinDNA hybrid nanostructure to redox signaling,and also provide theoretical insights into the applications of the hybrid nanosturcture in biomedical field.In conclusion,the binding of protein with polar NM can be regulated by the above three influential factors,which primarily occurs through adjustments to the polar interactions between protein and polar NM,including hydrogen bond,salt bridge,and electrostatic interactions.Therefore,the results of this thesis elucidate the important role of polar interactions in the regulation of the binding of protein with polar NM.And they can be better to further understand the molecular mechanism of the interaction between protein and polar NM,and provide theoretical insights into improving the biocompatibility of NMs and facilitating their applications in biomedical field.