High quality computational quantum chemistry modelling and design of the shape and properties of macromolecules

大分子形状和性质的高质量计算量子化学建模和设计

• 批准号: 839-2007
• 负责人: Mezey, Paul
• 金额: $ 3.89万
• 依托单位: Memorial University of Newfoundland
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2007
• 资助国家: 加拿大
• 起止时间: 2007-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=362464
• 关键词: quality; computational; quantum; chemistry; modelling

In biochemistry, biotechnology, medicinal chemistry, drug-design, polymer research, and nanotechnology, macromolecular computer modeling and design are becoming major tools. Most earlier macromolecular modeling techniques, however, are rather crude, such as the most popular fused-sphere models ignoring pi-bonding and finer details.New level of accuracy has become possible for detailed macromolecular, protein and nanomaterial modeling, by the development and extensive tests of the  ab initio quality ADMA  (Adjustable Density Matrix Assembler)  macromolecular quantum chemistry method. This linear-scaling method is likely to provide a wealth of new knowledge about the very extensive low electron density interactions within globular macromolecules, e,g. proteins, influencing, even determining the folding pattern, so important in protein structure and reactions. Up till now, these extensive low density ranges have been ignored by conventional fused sphere models, and have been inaccessible for study by conventional quantum chemistry methods, prohibitively expensive and unsuitable for macromolecules.The ADMA macromolecular quantum chemistry method, and shape analysis techniques will be applied to(i)  the study and understanding of the stabilizing role of low density contributions to the electronic cloud of macromolecules, e.g. in protein folding and supramolecular chemistry,(ii)  designing novel macromolecules by assembling surroundings-adjusted functional groups into a desired structure, a task especially suited for the assembly-based ADMA method.(iii) Basic research on molecular informatics, holographic density theorem will continue.Significant advances are expected in understanding and designing biomolecules and nanostructures, and solving actual problems of Canadian biotechnology and toxicology, both in academia and industry.

在生物化学、生物技术、药物化学、药物设计、聚合物研究和纳米技术中，大分子计算机建模和设计正在成为主要工具。然而，大多数早期的大分子建模技术都是相当粗糙的，比如最流行的熔融球模型忽略了π键和更精细的细节。随着从头计算质量的ADMA（可调密度矩阵组装器）大分子量子化学方法的发展和广泛的测试，新的精确度已经成为可能，用于详细的大分子、蛋白质和纳米材料的建模。这种线性标度方法很可能为球状大分子内广泛的低电子密度相互作用提供丰富的新知识。蛋白质，影响，甚至决定折叠模式，在蛋白质结构和反应中非常重要。到目前为止，这些广泛的低密度区域一直被传统的熔融球模型所忽略，并且无法用传统的量子化学方法进行研究，昂贵且不适合于大分子。ADMA大分子量子化学方法和形状分析技术将被应用于（i）研究和理解低密度贡献对大分子电子云的稳定作用，例如在蛋白质折叠和超分子化学中，（ii）通过将环境调节的官能团组装成期望的结构来设计新的大分子，这是特别适合于基于组装的ADMA方法的任务。(iii)将继续开展分子信息学、全息密度定理等基础研究，在理解和设计生物分子和纳米结构以及解决学术界和工业界加拿大生物技术和毒理学的实际问题方面有望取得重大进展。