【摘 要】
：
Influenza A (A/HxNy) is a signif-icant public health concern due to its high infectiousness and mortality.Neuraminidase,which interacts with sialic acid (SIA) in host cells,has become an essen-tial target since its highly con-served catalytic center struc
【机 构】
：
School of Physics and Electronics,Shandong Normal University,Jinan,250014,China
论文部分内容阅读
Influenza A (A/HxNy) is a signif-icant public health concern due to its high infectiousness and mortality.Neuraminidase,which interacts with sialic acid (SIA) in host cells,has become an essen-tial target since its highly con-served catalytic center structure,while resistance mutations have already generated.Here,a de-tailed investigation of the drug resistance mechanism caused by mutations was performed for subtype N9 (A/H7N9).Molecular dynamics simulation and alanine-scanning-interaction-entropy method (ASIE) were used to explore the critical dif-ferences between N9 and Zanamivir (ZMR) before and after R294K mutation.The results showed that the mutation caused the hydrogen bond between Arg294 and ZMR to break,then the hydrogen bonding network was disrupted,leading to weakened binding ability and resistance.While in wild type (A/H7N9WT),this hydrogen bond was initially stable.Mean-while,N9 derived from A/H11N9 was obtained as an R292K mutation.Then the relative binding free energy of N9 with five inhibitors (SIA,DAN,ZMR,G28,and G39) was predicted,basically consistent with experimental values,indicating that the calculated results were re-liable by ASIE.In addition,Arg292 and Tyr406 were hot spots in the A/H11N9WT-drugs.However,Lys292 was not observed as a favorable contributing residue in A/H11N9R292K,which may promote resistance.In comparison,Tyr406 remained the hotspot feature when SIA,ZMR,and G28 binding to A/H11N9R292K.Combining the two groups,we speculate that the resistance was mainly caused by the disruption of the hydrogen bonding network and the transformation of hotspots.This study could guide novel drug delivery of drug-resistant mutations in the treatment of A/HxN9.
其他文献
In this study,we investigated the structural and dy-namical properties of liquid water by using ab initio molecular dynamics simulation under periodic bound-ary conditions based on the fragment-based quantum mechanical approach.This study was carried out
In this work,we employ electronic structure calculations and nonadia-batic dynamics simulations based on many-body Green function and Bethe-Salpeter equation (GW/BSE) meth-ods to study excited-state properties of a zinc phthalocyanine-fullerene (ZnPc-C60)
Ion selectivity in protein binding sites is of great significance to bi-ological functions.Although additive force fields have been successfully applied to various protein-related studies,it is diffi-cult to well capture the subtle metal-protein interacti
The reaction H+SO2→OH+SO is important in the combustion and atmospheric chemistry,as well as the interstellar medium.It also represents a typical complex-forming reaction with deep complexes,serv-ing as an ideal candidate for testing various kinetics theo
建立快速溶剂萃取(ASE)–气相色谱–质谱(GC–MS)法测定土壤中苯胺、邻硝基苯胺、间硝基苯胺、对硝基苯胺、二硝基苯胺5种苯胺类化合物的方法.样品经丙酮–二氯甲烷混合溶剂(体积比为1:1)提取,用硅酸镁小柱净化,经无水硫酸钠脱水,氮吹浓缩至1.0 mL,用GC–MS法测定,外标法定量.5种苯胺类化合物的质量浓度在0.2～2.0μg/mL范围内与特征离子色谱峰面积具有良好的线性关系,相关系数均不小于0.995,方法检出限为0.7～5.7μg/kg.当空白土壤样品加标质量分数分别为60、140μg/kg时,
建立同时测定舒胆片中栀子苷、虎杖苷、柚皮苷和新橙皮苷含量的高效液相色谱法.选择Kromasil 100–5–C18柱(4.6 mm×250 mm,5μm)为分离柱,以乙腈–水为流动相,梯度洗脱,流量为1.0 mL/min,柱温为30℃,检测波长:0～13 min时为238 nm,13～17 min时为306 nm,17～25 min时为283 nm.栀子苷、虎杖苷、柚皮苷和新橙皮苷在各自的质量范围内与色谱峰面积呈良好的线性关系,相关系数均大于0.999,方法检出限为0.02062～0.04963 ng,定
Protein-protein interac-tions are vital for a wide range of biologi-cal processes.The in-teractions between the hypoxia-inducible factor and von Hippel Lin-dau (VHL) are attractive drug targets for ischemic heart disease.In order to disrupt this interac-t
In this work,the solidification of liq-uid iron with or without external magnetic field was investigated by us-ing two molecular dynamics methods,namely direct cooling and two-phase simulation.The influence of external magnetic field on the solidification
建立同时快速测定化妆品中7种双酚类化合物及其衍生物的超高效液相色谱–串联质谱方法.水剂化妆品采用正己烷–乙酸乙酯(体积比为1:1)溶液超声提取;粉类、膏霜乳液类、凝胶类化妆品采用乙酸乙酯超声提取,提取液经氮吹浓缩后用甲醇–水(体积比为1:1)溶液定容,用Waters XSelect HSS T3(100 mm×2.1μm,1.7μm)色谱柱分离,采用质谱多反应监测模式检测,色谱峰面积外标法定量.7种双酚类化合物及其衍生物的质量浓度在0.1～50.0 ng/mL范围内与色谱峰面积线性关系良好,相关系数均不小
Machine learning potentials are promising in atomistic sim-ulations due to their compara-ble accuracy to first-principles theory but much lower com-putational cost.However,the reliability,speed,and trans-ferability of atomistic machine learning potentials