Brownian Dynamics Simulations of Actins with Aldolase

使用醛缩酶对肌动蛋白进行布朗动力学模拟

• 批准号: 6594131
• 负责人: KATHRYN A. THOMASSON
• 金额: $ 14.02万
• 依托单位: UNIVERSITY OF NORTH DAKOTA
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-06-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6594131
• 关键词: actins; aldehyde lyase; bioenergetics; chemical reaction; computer simulation; enzyme complex; glyceraldehyde 3 phosphate dehydrogenase; mathematical model; molecular dynamics; protein isoforms; protein protein interaction

DESCRIPTION (provided by applicant): The cytoskeletal structure, F-actin, plays an important role in cellular metabolism by providing conditions for the high specificity of reactions within various metabolic pathways. Many glycolytic enzymes including fructose-1,6-bisphophsate aldolase (aldolase), glycerladehyde-3-phosphate dehydrogenase (GAPDH), and lactate dehydrogenase (LDH) bind actin reversibly. Other enzymes such as triose phosphate isomerase (TIM) bind indirectly through interactions with the enzymes that bind. The proposed study will use and enhance existing theoretical methods to better investigate the interaction of F-actin with glycolytic enzymes. The method of Brownian dynamics (BD) predicts the various kinds of complexes between F-actin and the glycolytic enzymes; BD also provides the relative stability of complexes by performing an automated forceguided exhaustive search. BD simulates the protein-protein associations in water as influenced by the ionic effects that mediate molecular interactions in physiological complexes. The simulations provide free energies of protein-protein associations. This work will expand the enzymes studied and continue to enhance the existing method as found in the program package MacroDox. The goals are: (1) to examine LDH and TIM interactions with F-actin and compare them to predictions for aldolase and GAPDH; (2) to reproduce experimentally observed factors on binding such as ionic strength, pH, and relative binding affinities; and (3) to treat enzyme-enzyme/F-actin complex interactions. The importance of the proposed study relates to the hypothesis that F-actin creates a structure in the cell cytoplasm upon which glycolytic enzymes associate and dissociate dynamically. These dynamic associations may be important to organizing the reactions in the glycolytic pathway and assembling an extensive complex of glycolytic enzymes. The outcome of the research would be an improved understanding of protein association with actin in solution. It will be a theoretical test for F-actin forming a framework for glycolytic enzymes to function in cells. It will further the understanding of the theory behind assembly of structures in the cytoplasmic matrix. Thus, the outcome of this research should have far-reaching implications for cytoplasmic structure and metabolic regulation.

描述（由申请人提供）：细胞骨架结构F-肌动蛋白通过为各种代谢途径内的高特异性反应提供条件，在细胞代谢中发挥重要作用。许多糖酵解酶包括果糖-1，6-二磷酸醛缩酶（醛缩酶）、甘油醛-3-磷酸脱氢酶（GAPDH）和乳酸脱氢酶（LDH）可逆地结合肌动蛋白。其他酶如磷酸丙糖异构酶（TIM）通过与结合的酶相互作用间接结合。这项研究将利用和增强现有的理论方法，以更好地研究F-肌动蛋白与糖酵解酶的相互作用。布朗动力学（BD）方法预测了F-肌动蛋白和糖酵解酶之间的各种复合物; BD还通过执行自动化的力引导穷举搜索来提供复合物的相对稳定性。BD模拟蛋白质-蛋白质在水中的关联，其受到介导生理复合物中分子相互作用的离子效应的影响。模拟提供了蛋白质-蛋白质缔合的自由能。这项工作将扩大所研究的酶，并继续加强在程序包MacroDox中发现的现有方法。目标是：（1）检查LDH和TIM与F-肌动蛋白的相互作用，并将其与醛缩酶和GAPDH的预测进行比较;（2）重现实验观察到的结合因素，如离子强度、pH值和相对结合亲和力;（3）处理酶-酶/F-肌动蛋白复合物相互作用。这项研究的重要性与以下假设有关：F-肌动蛋白在细胞质中产生一种结构，糖酵解酶在该结构上动态地缔合和解离。这些动态关联对于组织糖酵解途径中的反应和组装糖酵解酶的广泛复合物可能是重要的。这项研究的结果将是对蛋白质与肌动蛋白在溶液中的结合的更好的理解。这将是一个理论测试F-肌动蛋白形成一个框架，糖酵解酶在细胞中发挥作用。它将进一步理解背后的理论组装的结构在细胞质基质。因此，这项研究的结果应该对细胞质结构和代谢调节具有深远的影响。

项目成果

Brownian dynamics of interactions between aldolase mutants and F-actin.

醛缩酶突变体和 F-肌动蛋白之间相互作用的布朗动力学。

• DOI: 10.1002/jmr.599
• 发表时间: 2002
• 期刊: Journal of molecular recognition : JMR.
• 作者: Lowe,StephenL;Atkinson,DerekM;Waingeh,VictorF;Thomasson,KathrynA
• 通讯作者: Thomasson,KathrynA

Brownian dynamics of interactions between glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mutants and F-actin.

3-磷酸​​甘油醛脱氢酶 (GAPDH) 突变体和 F-肌动蛋白之间相互作用的布朗动力学。

• DOI: 10.1002/bip.10560
• 发表时间: 2004
• 期刊: Biopolymers.
• 作者: Waingeh,VictorF;Lowe,StephenL;Thomasson,KathrynA
• 通讯作者: Thomasson,KathrynA

Dipole interaction model predicted pi-pi* circular dichroism of cyclo(L-Pro)3 using structures created by semi-empirical, ab initio, and molecular mechanics methods.

偶极相互作用模型使用半经验、从头计算和分子力学方法创建的结构预测了 cyclo(L-Pro)3 的 pi-pi* 圆二色性。

• DOI: 10.1034/j.1399-3011.2003.00046.x
• 发表时间: 2003
• 期刊: The journal of peptide research : official journal of the American Peptide Society
• 作者: Lowe,SL;Pandey,RR;Czlapinski,J;Kie-Adams,G;Hoffmann,MR;Thomasson,KA;Pierce,KS
• 通讯作者: Pierce,KS

BD SIMULATIONS OF THE IONIC STRENGTH DEPENDENCE OF THE INTERACTIONS BETWEEN TRIOSE PHOSPHATE ISOMERASE AND F-ACTIN.

磷酸三糖异构酶和 F-肌动蛋白之间相互作用的离子强度依赖性的 BD 模拟。

• 发表时间: 2010
• 期刊: Journal of undergraduate chemistry research
• 作者: Schmidt,ElizabethSpanbauer;Forlemu,NevilleY;Njabon,EricN;Thomasson,KathrynA
• 通讯作者: Thomasson,KathrynA