Simulating Protein Structures, Complexes, And Dynamics
模拟蛋白质结构、复合物和动力学
基本信息
- 批准号:7733762
- 负责人:
- 金额:$ 73.38万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:
- 资助国家:美国
- 起止时间:至
- 项目状态:未结题
- 来源:
- 关键词:1-Phosphatidylinositol 4-KinaseAddressAlzheimer&aposs DiseaseArtsBenzodiazepine ReceptorBindingBinding SitesCollaborationsComplexComputer SimulationComputing MethodologiesCyclin-Dependent Kinase 5Dipotassium Salt Eosine Yellowish-EndopeptidasesEnzymesEosine YellowishEosine Yellowish-, Potassium, Sodium SaltFutureG-Protein-Coupled ReceptorsGene MutationGenerationsGoalsHIV Envelope Protein gp120Heat-Shock Proteins 90Homology ModelingHormonesHuman DevelopmentIonsLigand BindingLigandsMammary NeoplasmsManuscriptsMechanicsMelatoninMethodsModelingMolecular StructureMonoclonal AntibodiesNational Institute of Child Health and Human DevelopmentNational Institute of Drug AbuseNational Institute of Mental HealthNatureNeurodegenerative DisordersOpioid AnalgesicsOpioid ReceptorPaperPathway interactionsPeptide HydrolasesPeripheralPositron-Emission TomographyPreparationProlactinProlactin ReceptorProteinsPublicationsPublishingQuantum MechanicsRangeReportingResearchSeriesSerotoninSignaling MoleculeSimulateSolutionsSolventsSpecificityStagingStructureStructure-Activity RelationshipStudy modelsSystemTechniquesThermodynamicsVenezuelan Equine EncephalomyelitisWorkaqueousbasecomputer studiesdesignenzyme mechanismextracellularimprovedinhibitor/antagonistinterestmolecular dynamicsmolecular mechanicsmolecular modelingmutantnovelprotein structurequantumsimulationskin disorderstructural biologyvirology
项目摘要
We have continued to develop, implement, and apply simulation methods in computational studies of the energetics and dynamics of biomolecular systems. We are working to refine a continuum description of macromolecular solvation in terms of polar, nonpolar, and solvent-structure effects. A detailed understanding of aqueous solutions and their effects on biomolecules should expedite future improvements to a continuum description, and two papers have been published reporting atomistic simulations of ion clusters in solution (SA Hassan).
We also model proteins based on homology and work to improve the generation and refinement of such models. With NICHD, we have published a study of the inhibitor sensitivities of type-III phosphatidylinositol 4-kinase enzymes (A Balla et al.). Collaborating with OD, we modeled a deletion mutant of the HIV envelope glycoprotein gp120 for which exposure of the CD4 binding site leads to enhanced binding of two monoclonal antibodies. This study was published in Virology (I Berkower et al.). Additional modeling studies of gp120 and of Venezuelan equine encephalitis (VEE) protease are in preliminary stages. With NCI, we are preparing a manuscript in which homology modeling is used to investigate genetic mutations associated with skin disease.
In collaboration with NIMH and NHLBI, we published a study describing reliable ways of determining the transition state of peripheral benzodiazepine receptor ligands (YS Lee et al.). Building on this study, we are applying quantum mechanical calculations to understand the mechanisms involved in synthesizing novel PET ligands.
With NIDA, we are studying the structure-activity relationships of opioid-receptor ligands, in attempts to design and synthesize novel opioid analgesics. One paper was published (J Zezula et al.), one has been submitted, and a third is in preparation.
Ongoing collaborative research with NCI includes the design and synthesis of a new series of HSP90 inhibitors.
With NICHD, we are studying the dynamics and energetics of AANAT, the first enzyme in the serotonin-melatonin conversion pathway, and a paper was published (J Pavlicek et al.). Also with NICHD, we have submitted a manuscript for publication in which Monte Carlo and molecular dynamics simulations were used to study the structural nature of prolactin-receptor interactions and the specificity of binding and recognition. Prolactin is a hormone that has been implicated in the development of human breast tumors.
With NINDS, we are using computer modeling to better understand the structural and dynamical basis for the function of cyclin-dependent kinase 5 (cdk5). The deregulation of cdk5 may be involved in neurodegenerative diseases such as Alzheimer's disease.
We have also been working to develop computational methods for obtaining reliable structures of G protein coupled receptors (GPCRs). Realistic models could be used to investigate the interactions of GPCRs with extracellular and intracellular signaling molecules.
我们继续发展,实施和应用模拟方法在生物分子系统的能量学和动力学的计算研究。我们正在努力完善大分子溶剂化在极性、非极性和溶剂结构效应方面的连续描述。对水溶液及其对生物分子的影响的详细了解将加速未来对连续体描述的改进,并且已经发表了两篇论文,报告了溶液中离子团簇的原子模拟(SA Hassan)。
项目成果
期刊论文数量(21)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Identification of substrate binding site of cyclin-dependent kinase 5.
细胞周期蛋白依赖性激酶 5 底物结合位点的鉴定。
- DOI:10.1074/jbc.274.14.9600
- 发表时间:1999
- 期刊:
- 影响因子:0
- 作者:Sharma,P;Steinbach,PJ;Sharma,M;Amin,ND;BarchiJr,JJ;Pant,HC
- 通讯作者:Pant,HC
Population dynamics of a pathogen: the conundrum of vivax malaria.
- DOI:10.1007/s12551-010-0034-3
- 发表时间:2010-08
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Dynamics of proton transfer in bacteriorhodopsin.
细菌视紫红质中质子转移的动力学。
- DOI:10.1021/ja036115v
- 发表时间:2004
- 期刊:
- 影响因子:15
- 作者:Lee,Yong-Sok;Krauss,Morris
- 通讯作者:Krauss,Morris
Biological effect of a novel mutation in the third leucine-rich repeat of human luteinizing hormone receptor.
人黄体生成素受体第三个富含亮氨酸的重复序列中新突变的生物学效应。
- DOI:10.1210/me.2005-0510
- 发表时间:2006
- 期刊:
- 影响因子:0
- 作者:Leung,MichaelYiu-Kwong;Steinbach,PeterJ;Bear,Deborah;Baxendale,Vanessa;Fechner,PatriciaY;Rennert,OwenM;Chan,Wai-Yee
- 通讯作者:Chan,Wai-Yee
Solid-state NMR evidence for an antibody-dependent conformation of the V3 loop of HIV-1 gp120.
HIV-1 gp120 V3 环的抗体依赖性构象的固态 NMR 证据。
- DOI:10.1038/5827
- 发表时间:1999
- 期刊:
- 影响因子:0
- 作者:Weliky,DP;Bennett,AE;Zvi,A;Anglister,J;Steinbach,PJ;Tycko,R
- 通讯作者:Tycko,R
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PETER J STEINBACH的其他文献
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{{ truncateString('PETER J STEINBACH', 18)}}的其他基金
Simulating Protein Structures, Complexes, And Dynamics
模拟蛋白质结构、复合物和动力学
- 批准号:
6540964 - 财政年份:
- 资助金额:
$ 73.38万 - 项目类别:
Simulating Protein Structures, Complexes, And Dynamics
模拟蛋白质结构、复合物和动力学
- 批准号:
9146125 - 财政年份:
- 资助金额:
$ 73.38万 - 项目类别:
Simulating Protein Structures, Complexes, And Dynamics
模拟蛋白质结构、复合物和动力学
- 批准号:
10255220 - 财政年份:
- 资助金额:
$ 73.38万 - 项目类别:
Simulating Protein Structures, Complexes, And Dynamics
模拟蛋白质结构、复合物和动力学
- 批准号:
6832604 - 财政年份:
- 资助金额:
$ 73.38万 - 项目类别:
SIMULATING PROTEIN STRUCTURES, COMPLEXES, AND DYNAMICS
模拟蛋白质结构、复合物和动力学
- 批准号:
6431908 - 财政年份:
- 资助金额:
$ 73.38万 - 项目类别:
Simulating Protein Structures, Complexes, And Dynamics
模拟蛋白质结构、复合物和动力学
- 批准号:
7145142 - 财政年份:
- 资助金额:
$ 73.38万 - 项目类别:
Simulating Protein Structures, Complexes, And Dynamics
模拟蛋白质结构、复合物和动力学
- 批准号:
7296872 - 财政年份:
- 资助金额:
$ 73.38万 - 项目类别:
Simulating Protein Structures, Complexes, And Dynamics
模拟蛋白质结构、复合物和动力学
- 批准号:
6675525 - 财政年份:
- 资助金额:
$ 73.38万 - 项目类别:
SIMULATING PROTEIN STRUCTURES, COMPLEXES, AND DYNAMICS
模拟蛋白质结构、复合物和动力学
- 批准号:
6289572 - 财政年份:
- 资助金额:
$ 73.38万 - 项目类别:
Simulating Protein Structures, Complexes, And Dynamics
模拟蛋白质结构、复合物和动力学
- 批准号:
7593228 - 财政年份:
- 资助金额:
$ 73.38万 - 项目类别:
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