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Search Results: 1 - 10 of 384268 matches for " p53-MDMX相互作用;分子动力学;MM-PBSA;结合自由能<br>p53-MDMX Interaction "
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肿瘤蛋白MDMX与抑制剂PMI作用机制的分子动力学研究
Molecular Dynamics Insight into the Interaction Mechanism of Inhibitor PMI with MDMX
 [PDF]

程伟渊, 梁志强, 王伟, 伊长虹, 王克彦, 李洪云, 陈建中
Hans Journal of Computational Biology (HJCB) , 2012, DOI: 10.12677/hjcb.2012.23003
Abstract: 恢复抑癌蛋白p53的功能已经成为一种治疗癌症的新途径。本文采用分子动力学模拟和MM-PBSA方法计算了抑制剂PMI与肿瘤蛋白MDMX的结合自由能。结果表明范德华相互作用驱动了PMIMDMX的结合。同时也使用基于残基对的自由能分解方法计算了残基残基相互作用,结果不仅表明PMI5个残基能与MDMX产生强烈的相互作用,而且也表明CH-CHCH-ππ-π相互作用主导了PMIMDMX疏水性裂缝中的结合。我们期望这个研究能为抑制p53-MDMX相互作用药物的研发提供理论上的启示。
Restoration of p53 function is considered to be a new therapeutic strategy for anti-cancers. Molecular Dynamics (MD) simulations coupled with Molecular
抑制剂8CA与脂肪细胞脂肪酸结合蛋白(A-FABP)结合模式的分子动力学研究
Insight into binding mode of inhibitor 8CA to A-FABP based on molecular dynamics simulation

尹妍妍,梁志强,王伟,伊长虹,李洪云,赵娟,张庆刚
- , 2016,
Abstract: 脂肪细胞脂肪酸结合蛋白A-FABP(Adipocyte fatty-acid binding protein)是治疗脂质调节生物过程相关疾病的重要靶标. 分子动力学模拟和MM-PBSA方法被采用研究抑制剂8CA与A-FABP结合模式. 研究结果表明静电相互作用和范德华作用驱动了抑制剂8CA与A-FABP的结合。基于残基的能量分解表明抑制剂8CA与R126间的极性相互作用为抑制剂与A-FABP的结合提供了重要贡献. 该残基与8CA的相互作用较好地稳定了抑制剂与A-FABP复合物的稳定性. 我们期望这个研究能为治疗炎症、动脉硬化和代谢病药物设计提供一定的理论指导。
Adipocyte fatty-acid binding protein (A-FABP) is an important target of drug designs treating some diseases related to lipid-mediated biology. Molecular dynamics (MD) simulations coupled with molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) calculation were carried out to study the binding mode of 8CA to A-FABP. The results show that electrostatics and van der Waals interactions drive the binding of 8CA to A-FABP. The calculation from residue-based free energy decomposition suggests that the polar interaction of 8CA with the residue R126 provides an important contribution to the 8CA binding. This polar interaction plays a key role in the stabilization of 8CA/A-FABP complex. We expect that this study can contribute some theoretical guidance for design of potent inhibitors within the fields of metabolic disease, inflammation and atherosclerosis.
分子动力学研究抗体SPE7与抗原Alizarin red的相互作用机制
Insight into interaction mechanism of antibody SPE7 with antigen alizarin red by molecular dynamics simulations

刘进庆,梁志强,王伟,伊长虹,李洪云,赵娟,张庆刚
- , 2017,
Abstract: 研究抗原与抗体的相互作用机制在治疗与抗体相关疾病药物的研发中起到重要作用. 采用分子动力学模拟和MM-PBSA(molecular mechanics-Poisson Boltzmann surface area)以及溶解相互作用能SIE(solvated interaction energy)方法研究了抗原Alizarin red(AZN)与抗体SPE7的结合模式. 研究结果证明范德华作用主导了抗原AZN与抗体SPE7的相互作用. 基于残基能量分解的计算表明抗原AZN能与残基H-W35、H-Y105、L-Y34和L-W93产生较强的相互作用, 此结果表明AZN与SPE7分离残基间的π-π相互作用驱动了AZN与SPE7的结合. 期望这个研究能为治疗与抗体相关疾病药物的研发提供重要的理论指导.
The interaction mechanism of antigens with antibodies plays an important role in development of drugs curing diseases related with antibodies. In this work, molecular dynamics simulations combined with molecular mechanics-Poisson Boltzmann surface area (MM-PBSA) method and solvated interaction energy (SIE) were carried out to study the binding mode of antigen Alizarin red (AZN) to antibody SPE7. The results show that van der Waals interaction is a main force to control the interaction of AZN with SPE7. The calculations from residue-based free energy decomposition indicates that the π-π interaction of AZN with separate residues in SPE7 drives the binding of AZN to SPE7. More detailed, AZN produces strong interactions with the residues H-W35、H-Y105、L-Y34 and L-W93 in SPE7. We expect that this work can provide theoretical guidance for the development of drugs targeting the interactions of antigens with antibodies
Y220C突变体影响p53C蛋白质构象转换的分子动力学模拟
Effect of Y220C Mutant on the Conformational Transition of p53C Probed by Molecular Dynamics Simulation

沈洪辰,丁吉勇,李丽,刘夫锋,()
- , 2016, DOI: 10.3866/PKU.WHXB201606224
Abstract: p53是迄今发现突变频率最高的一种肿瘤抑制蛋白质,突变会导致p53抑癌功能丧失并诱导癌症的发生。绝大多数的突变发生在p53的核心DNA结合区域(p53C),其中Y220C是研究较多的一种突变体。虽然已有研究表明该突变能够降低p53C的结构稳定性,但其影响p53C构象转换的分子机制尚不清晰。本文利用分子动力学(MD)模拟方法研究了p53C突变体Y220C(p53C-Y220C)的结构变化,发现Y220C突变主要影响Y220C cluster区域(包括残基138-164和215-238),且Y220C突变减少了Y220C cluster的β-折叠含量。进一步分析发现,Y220C突变不仅直接破坏突变氨基酸与周围氨基酸Leu145和Thr155之间的氢键,而且降低了Y220C cluster区域的折叠片S3和S8之间的氢键数量,使Y220C突变所形成的亲水性空腔变大,加速了水分子进入该蛋白质内部,并最终导致了p53C-Y220C变性。MD模拟结果揭示了Y220C突变影响p53C结构转换的分子机制,该研究对p53C-Y220C突变体高效稳定剂的筛选和设计具有重要意义。
At present, p53 is the tumor suppressor protein with the highest known frequency of mutation. Mutations in p53 will lead to the loss of its anti-cancer function and initiate cancers. The majority of the mutations in p53 are located in its core DNA binding domain (p53C). One of the most frequent mutation in p53C is Y220C. However, the molecular mechanism of the conformational transition of the Y220C mutant of p53C remains unclear, although it is known that the Y220C mutant greatly decreases the stability of p53C. In this study, molecular dynamics (MD) simulations are used to probe the conformational transition of the Y220C mutant of p53C. The Y220C cluster including residues 138-164 and 215-238, which are strongly affected by the mutant, is identified. The Y220C mutant decreases the content of β-sheets in the Y220C cluster. The Y220C mutation not only disrupts the hydrogen bonds between the mutated residue and surrounding residues such as Leu145 and Thr155, but also weakens the hydrogen bonds between S3 and S8 of the Y220C cluster. This causes the volume of the hydrophilic cavity to increase, accelerating water molecule entry into the cavity, which eventually unfolds the protein. The above MD results explain the molecular mechanism of the Y220C mutant in the conformational transition of p53C. These findings will benefit virtual screening and design of novel stabilizers of the mutant Y220C of p53C
MOLECULAR DYNAMICS RESEARCH ON R175 RESIDUE SUBSTITUTION IN P53 PROTEIN
P53蛋白质R175残基替换的分子动力学研究

ZHANG Yan,SHI Xiu-fan,LIU Ci-quan,
张彦
,石秀凡,刘次全

生物物理学报 , 2000,
Abstract: The molecular dynamics research of the core domain of p53 protein crystal structure shows that besides the stability in biochemistry this domain also shows a high stability in molecular mechanics. Based on this work, we substituted the residue R175 with some other amino acids and performed molecular dynamics researches separately. The results show that substitution of R175 causes a relax tendency between loop2 and 3 domains, leading to an alteration of the whole conformation of p53 core domain and ruining its stability. This research visually explains the mechanism of p53 changes in immunological and biochemical reactions, which are caused by R175 substitutions leading to the 3-D structure variations.
甜菜夜蛾细胞色素P450(CYP9A11)与3种杀虫剂的结合机理研究
Study on binding mechanisms of cytochrome P450(CYP9A11) withthree pesticides in Spodoptera exigua

邓培渊,李玉华,袁伟,王林青,李长看
- , 2016,
Abstract: 细胞色素P450(以下简称CYP)与昆虫的抗药性密切相关。本研究运用AutoDock分子对接技术和分子力学泊松-波尔兹曼表面积法(molecular mechanics Poisson-Boltzmann surface area,MM-PBSA)结合自由能计算方法,分析了甜菜夜蛾CYP9A11与3种杀虫剂结合的作用位点、作用力类型和大小。结果表明:CYP9A11与毒死蜱结合形成两个氢键,有8个氨基酸残基参与形成疏水作用力,二者结合自由能为-3659.80 kJ/mol;CYP9A11与灭多威结合形成5个氢键,有3个氨基酸残基形成疏水作用力,结合自由能为-470.92 kJ/mol;CYP9A11中有7个氨基酸残基与氯氰菊酯结合形成疏水作用力,结合自由能为-473.44 kJ/mol。范德华力是CYP9A11与毒死蜱结合的主要驱动力,极性溶剂化能是CYP9A11与氯氰菊酯和灭多威结合的主要驱动力,这些结果为阐明甜菜夜蛾CYP9A11与3种杀虫剂的结合机理提供了参考。
Cytochrome P450 has been well known to play crucial roles in pesticide resistance in insects. In this study, binding sites, type and size of the driving force between cytochrome P450(CYP9A11) in Spodoptera exigua and three pesticides were investigated by AutoDock molecular docking and molecular mechanics Poisson-Boltzmann surface area(MM-PBSA), MM-PBSA free energy calculation. The results showed as follows:when CYP9A11 combined with chlorpyrifos, two hydrogen bonds and eight hydrophobic residues were formed, and the binding free energy was -3659.80 kJ/mol. Five hydrogen bonds and three hydrophobic residues were formed when CYP9A11 combined with methomyl, and the binding free energy was -470.92 kJ/mol. Seven hydrophobic residues formed when CYP9A11 combined with cypermethrin and the binding free energy was -473.44 kJ/mol. The van der Wals force was the main driving force of the docking between CYP9A11 and chlorpyrifos, methomyl and cypermethrin. The main driving force of binding to CYP9A11 was the polar solvation energy. These data could serve as references of illuminating the binding mechanisms of the above mentioned three pesticides with CYP9A11 in S. exigua.
谷氨酰胺结合蛋白的分子动力学模拟和自由能计算
胡建平,孙庭广,陈慰祖,王存新
化学学报 , 2006,
Abstract: 谷氨酰胺结合蛋白(Glutamine-bindingprotein,GlnBp)是大肠杆菌透性酶系统中一个细胞外液底物专一性结合蛋白,对于细胞外液中谷氨酰胺(Gln)的运输和传递至关重要.本文运用分子动力学(Moleculardynamics,MD)模拟采样,考察了GlnBp关键残基与底物Gln之间的相互作用和GlnBp两条铰链的功能差别;并采用MM-PBSA方法计算了GlnBp与底物Gln的结合自由能.结果表明Ph13,Phe50,Thr118和Ile69与底物Gln的范德华相互作用和Arg75,Thr70,Asp157,Gly68,Lys115,Ala67,His156与底物Gln的静电相互作用是结合Gln的主要推动力;复合物的铰链区85~89柔性大,对构象开合提供了结构基础;而铰链区181~185柔性小,其作用更多是在功能上把底物Gln限制在口袋中;自由能预测值与实验值吻合.本研究很好地解释了GlnBp结构与功能的关系,为进一步了解GlnBp的开合及转运Gln的机制提供了重要的结构信息.
分子动力学模拟研究质子化态在HIV-1Protease-Indinavir复合物中的作用
时术华,扈国栋,陈建中,张少龙,张庆刚
化学学报 , 2009,
Abstract: I型人体免疫缺陷病毒(HIV-1)蛋白酶中Asp25/Asp25'的质子化对于理论研究HIV-1蛋白酶和抑制剂的作用机制以及氨基酸变异对抗药性的影响有重要意义.分别对Protease-Indinavir(PR-IDV)复合物的六种可能的质子化态进行了5ns的分子动力学模拟,分析了不同状态对动力学特征和结构的影响,用molecularmechanics/Possion-Boltzmansurfacearea(MM-PBSA)方法计算了PR和IDV在各种状态下的结合自由能.计算结果说明A链Asp25的OD2的质子化是最为可能的状态.对PR-IDV复合物中起到媒介作用的水分子与PR-IDV复合物形成的氢键进行了分析,分析结果说明不同的质子化态对水分子在PR-IDV复合物中所起的媒介作用没有影响,这一结果与我们先前对PR-BEA369复合物的研究不同.我们的研究结果为更高效的PR抑制剂的设计以及PR氨基酸变异对药物抗药性的研究提供了理论上的指导.
HIV-1蛋白酶与抑制剂作用的结合自由能计算
伊长虹,张庆刚
化学学报 , 2010,
Abstract: HIV-1蛋白酶是治疗艾滋病的重要靶标酶之一.采用分子动力学模拟,运用MM-PBSA方法计算了HIV-1蛋白酶与三个抑制剂BE4,BE5和BE6的结合自由能,结果表明抑制剂P1/位置的苄基上双氟原子的不同位置对结合自由能产生不同的影响.通过能量分解的方法考察了HIV-1蛋白酶的主要残基与三个抑制剂间的相互作用与识别,结果表明三个抑制剂以相同的作用模式与HIV-1蛋白酶结合,计算结果与实验结果基本吻合.
CDK2-抑制剂结合自由能计算
蒋勇军,曾敏,周先波,邹建卫,俞庆森
化学学报 , 2004,
Abstract: 细胞周期蛋白依赖性激酶Ⅱ(cyclin-dependentkinase2,CDK2)是一种重要的治疗癌症的靶标.本文中采用分子动力学取样,运用MM-PBSA/GBSA两种方法计算了CDK2-NU6102复合物的绝对结合自由能.通过能量分解的方法考察了CDK2大分子主要残基与配体NU6102之间的相互作用和识别.
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