Lung Surfactant Pathologies: Study of the Formation of Biomolecular Aggregates
肺表面活性剂病理学:生物分子聚集体形成的研究
基本信息
- 批准号:7284010
- 负责人:
- 金额:$ 17.24万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2007
- 资助国家:美国
- 起止时间:2007-05-01 至 2011-04-30
- 项目状态:已结题
- 来源:
- 关键词:Acute Lung InjuryAffectAirAlveolarAmino Acid SequenceAmino AcidsArtsCerealsChargeCholesterolCodeCommunitiesComputational TechniqueComputer SimulationComputer softwareConditionCoupledDegenerative DisorderDevelopmentDiseaseEnvironmentEquilibriumInfantIonic StrengthsLipidsLipoidosisLiteratureMechanicsMethodsModelingModificationMolecularMonitorMutationNeonatal MortalityNewborn Respiratory Distress SyndromePathologyPeptide Sequence DeterminationPhosphatidyl glycerolPhosphatidylglycerolsPropertyProteinsPulmonary Alveolar ProteinosisPulmonary SurfactantsResearchSamplingSolutionsStandards of Weights and MeasuresStructureSurfaceSurface TensionSystemTechniquesTemperatureThermodynamicsWateralveolar lamellar bodybasemolecular dynamicsmonolayernovel strategiesprogramsprotein aggregateprotein aggregationresearch studysimulationsurfactant
项目摘要
Pulmonary surfactant is a surface active material composed of a lipids/protein mixture that forms layered
structures, i.e. Langmuir monolayer at the alveolar air/water interface and bilayers in lamellar bodies. The
typical compositions of pulmonary surfactant are 50% of dipalmitolphosphotidylcholine (DPPC), 25%
unsaturated phosphotidylcholine, 12% of the negatively charged phosphatidylglycerol (PG), and 8% of
surfactant proteins. The remaining 5% includes other type of lipids and cholesterol. Various pathological
conditions have been associated with abnormal composition levels of pulmonary surfactants. For example,
an insufficient amount of pulmonary surfactants in premature or newly born infants causes respiratory
distress syndrome, which is a major cause of neonatal mortality. Large quantities of certain surfactant
proteins have been associated to the formation of amyloidal fibrils causing a condition termed pulmonary
alveolar proteinosis (PAP). Also, inappropriate concentration of lipids in the lung surfactant can induce lipid
aggregation, causing degenerative diseases such as acute lung injury and lipidosis. The detailed molecular
mechanism for the aggregation of the various components of lung surfactant is not fully understood. We
hypothesize that aggregation of surfactant proteins and/or lipids will occur at certain lipid layered-structure
and thermodynamic states (composition, temperature and surface tension). The main reason for our
hypothesis is that intermolecular forces in the lipidic-layered environment can promote the necessary
structural changes in proteins, and hence the formation of aggregates. We also hypothesize that general
rules can be derived allowing us to make predictions regarding the formation of aggregates in lung
surfactants. To investigate our hypotheses, we propose to use state-of-the-art computer simulations.
Specifically, coarse-grained, united, and all-atom interparticle potentials will be used and/or developed that
permit an accurate description of the forces acting on the systems being investigated. Computational
techniques such as Monte Carlo and Molecular Dynamics, coupled to efficient sampling techniques, will be
used to determine the properties and conditions for the formation of aggregates in pulmonary surfactants.
The research will permit the elucidation of the mechanism of formation of lipid/protein aggregates in lung
surfactants and the correlation of this formation to pathologies. This correlation will help to the development
of new approaches for the treatment of PAP and lipidosis, as well as other protein aggregation related
diseases.
肺表面活性剂是一种由脂质/蛋白质混合物组成的表面活性物质,呈层状
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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GUSTAVO E LOPEZ-QUINONES其他文献
GUSTAVO E LOPEZ-QUINONES的其他文献
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{{ truncateString('GUSTAVO E LOPEZ-QUINONES', 18)}}的其他基金
Novel Methodologies for the Preservation (and Recovery) of Proteins at Low Temperature
低温保存(和回收)蛋白质的新方法
- 批准号:
10677786 - 财政年份:2021
- 资助金额:
$ 17.24万 - 项目类别:
Novel Methodologies for the Preservation (and Recovery) of Proteins at Low Temperature
低温保存(和回收)蛋白质的新方法
- 批准号:
10088682 - 财政年份:2021
- 资助金额:
$ 17.24万 - 项目类别:
Novel Methodologies for the Preservation (and Recovery) of Proteins at Low Temperature
低温保存(和回收)蛋白质的新方法
- 批准号:
10460399 - 财政年份:2021
- 资助金额:
$ 17.24万 - 项目类别:
PROTEIN AGGREGATION AND AMYLOIDAL FIBRIL FORMATION IN NANOPOLYMERIC
纳米聚合物中的蛋白质聚集和淀粉样纤维形成
- 批准号:
8360155 - 财政年份:2011
- 资助金额:
$ 17.24万 - 项目类别:
Lung Surfactant Pathologies: Study of the Formation of Biomolecular Aggregates
肺表面活性剂病理学:生物分子聚集体形成的研究
- 批准号:
7816960 - 财政年份:
- 资助金额:
$ 17.24万 - 项目类别:
Lung Surfactant Pathologies: Study of the Formation of Biomolecular Aggregates
肺表面活性剂病理学:生物分子聚集体形成的研究
- 批准号:
7625992 - 财政年份:
- 资助金额:
$ 17.24万 - 项目类别:
Lung Surfactant Pathologies: Study of the Formation of Biomolecular Aggregates
肺表面活性剂病理学:生物分子聚集体形成的研究
- 批准号:
8065497 - 财政年份:
- 资助金额:
$ 17.24万 - 项目类别:
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