Computational tools for the prediction of protein orientations on material surfac

用于预测材料表面蛋白质方向的计算工具

• 批准号: 8445083
• 负责人: Wendy E Thomas
• 金额: $ 7.73万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8445083
• 关键词: Albumins; Algorithms; Amino Acids; Antibodies; Biological Assay; Biotechnology; Collaborations; Complement; Complex; Computer software; Data; Data Analyses; Development; Elements; Fibrinogen; Film; Frequencies; G-substrate; Gambling; Generations; Imagery; Ions; Laboratories; Letters; Literature; Measures; Medical Device Designs; Membrane Proteins; Modeling; Molecular; Molecular Conformation; Muramidase; Myoglobin; Phase; Physiologic pulse; Process; Proteins; Proteus; Research Personnel; Roentgen Rays; Running; Software Tools; Specialist; Specific qualifier value; Spectrometry; Spectrometry, Mass, Secondary Ion; Spectrum Analysis; Structure; Sum; Surface; Techniques; Testing; Time; Visual; absorption; base; computerized data processing; computerized tools; design; improved; insight; interest; molecular dynamics; public health relevance; research study; simulation; three dimensional structure; tool; user-friendly; von Willebrand Factor; web site

DESCRIPTION (provided by applicant): Understanding the orientation of proteins on material surfaces is of crucial importance for the design of material surfaces with applications in biotechnology. However, the determination of protein orientation at atomic level of detail remains a challenge. Various surface analysis techniques, like flight secondary ion mass spectrometry, sum frequency generation vibrational spectrometry and near-edge X-ray absorption fine structure, have been developed to probe the orientation of proteins adsorbed onto surfaces. However, the spectra generated by this type of experiments can be very complex and extrapolating a result can be difficult if not impossible without suitable post-processing software. In this project, software tools are developed which make use of available three-dimensional structures of proteins to predict the spectrum that would be measured given a particular orientation of the protein on a surface. Furthermore, a publicly accessible online server will be setup which, using Monte Carlo simulations, will predict the orientation of a protei uploaded by a user on a selected surface. The Monte Carlo search can be guided by including available experimental data in order to refine a model suggested by the experiments or discriminate the most likely orientation when contradicting models are suggested by different techniques. If no experimental data is present, the server will provide an estimate of the protein orientation that can be either used to generate hypotheses or as the starting conformation for more complex calculations of the protein-surface interaction.

描述（由申请人提供）：了解材料表面上蛋白质的方向对于在生物技术中应用的材料表面设计至关重要。但是，在原子级别的蛋白质取向的确定仍然是一个挑战。已经开发了各种表面分析技术，例如飞行次级离子质谱，总和频率产生振动光谱和近边缘X射线吸收细胞，以探测吸附在表面上的蛋白质的方向。但是，这种类型的实验产生的光谱可能非常复杂，如果没有合适的后处理软件，那么不可能即使不是不可能的结果。在此项目中，开发了软件工具，该工具利用可用的三维蛋白质结构来预测鉴于表面上蛋白质的特殊取向将测量的光谱。此外，将设置可公开访问的在线服务器，使用Monte Carlo模拟，将预测用户在所选表面上上传的Protei的方向。可以通过包括可用的实验数据来指导蒙特卡洛搜索，以完善实验建议的模型，或在不同技术提出与模型相矛盾时歧视最可能的方向。如果不存在实验数据，则服务器将提供蛋白质取向的估计值，该蛋白质取向可用于生成假设，也可以作为起始构象，以进行更复杂的蛋白质表面相互作用。