Carbohydrate Force Field for Molecular Recognition

碳水化合物是地球上最丰富的生物聚合物。它们的生物学功能包括燃料、能量储存、代谢中间体、结构作用以及重要的分子识别，包括在疫苗、细胞-细胞识别和细菌毒素的致病活性中的作用。因此，详细了解碳水化合物的结构-功能 关系将允许更好地理解各种生物现象。探索这些结构-功能关系的理论方法提供了巨大的潜力。该研究将增强我们对碳水化合物结构性质的理解，以及在研究碳水化合物，特别是那些参与分子识别的理论方法的实用性。这些目标将通过首先调查 通过量子力学（QM）计算，已知对单糖和二糖的构象性质很重要的笨拙和异头效应。QM计算的信息将为碳水化合物的经验力场的发展奠定基础，该力场与蛋白质，脂质和核酸的CHARMM力场兼容，从而允许在非均质系统中对碳水化合物进行计算研究 包括糖蛋白和糖脂。优化的力场参数将通过分子动力学（MD）模拟研究的生物有趣的含碳水化合物的系统，实验数据是可用的。完成拟议的研究后，将更好地了解碳水化合物的结构特性，包括疫苗和细菌毒素在内的非均质系统中的单糖、多糖和碳水化合物。此外，一个新的经验力场碳水化合物将提供给科学界。与蛋白质、脂质和核酸的可用力场相容的碳水化合物力场的可用性将极大地增强计算方法对这些的适用性。 生物必需分子，促进治疗剂、疫苗和反恐剂的合理设计。

Carbohydrates are the most abundant biopolymers on earth. Their biological functions include fuels, energy storage, metabolic intermediates, structural roles and, importantly, molecular recognition, including roles in vaccines, cell-cell recognition and the pathogenic activity of bacterial toxins. Accordingly, detailed knowledge of carbohydrate structure-function relationships would allow for better understanding of a variety of biological phenomena. To explore these structure-function relationships theoretical approaches offer great potential. The proposed study will enhance both our understanding of the structural properties of carbohydrates as well as the utility of theoretical methods in studying carbohydrates, especially those involved in molecular recognition. These goals will be achieved by first investigating the gauche and anomeric effects, known to be important for the conformational properties of mono- and disaccharides, via quantum mechanical (QM) calculations. Information from the QM calculations will lay the groundwork for the development of an empirical force field for carbohydrates that is compatible with the CHARMM force fields for proteins, lipids and nucleic acids, thereby allowing for computational studies of carbohydrates in heterogeneous systems including glycoproteins and glycolipids. The optimized force field parameters will be validated via molecular dynamics (MD) simulation studies of biologically interesting carbohydrate-containing systems for which experimental data are available. Upon completion of the proposed study a better understanding of the structural properties of carbohydrates, ranging for monosaccharides, polysaccharides and carbohydrates in heterogeneous systems, including vaccines and bacterial toxins, will be obtained. In addition, a new empirical force field for carbohydrates will be made available to the scientific community. The availability of a carbohydrate force field that is compatible with available force fields for proteins, lipids and nucleic acids will greatly enhance the applicability of computational approaches to these biologically essential molecules, facilitating the rational design of therapeutic agents, vaccines and counterterrorism agents.