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）：了解蛋白质在材料表面上的方向对于生物技术应用的材料表面设计至关重要。然而，在原子水平细节上确定蛋白质方向仍然是一个挑战。各种表面分析技术，如飞行二次离子质谱、和频振动光谱和近边X射线吸收精细结构，已被开发用于探测吸附在表面上的蛋白质的方向。然而，此类实验生成的光谱可能非常复杂，如果没有合适的后处理软件，推断结果即使不是不可能，也可能很困难。在该项目中，开发的软件工具利用可用的蛋白质三维结构来预测在给定表面上蛋白质的特定方向的情况下将测量的光谱。此外，将设置一个可公开访问的在线服务器，该服务器将使用蒙特卡罗模拟来预测用户在选定表面上上传的蛋白质的方向。蒙特卡罗搜索可以通过包括可用的实验数据来指导，以便改进实验建议的模型，或者当不同技术建议矛盾的模型时区分最可能的方向。如果不存在实验数据，服务器将提供蛋白质方向的估计，该估计可用于生成假设或作为蛋白质-表面相互作用的更复杂计算的起始构象。