MOLECULAR STRUCTURE OF ANIMAL VIRUSES AND CELLS BY COMPUTATIONAL ANALYSIS

疾病及其治疗的基础在于知识和 理解蛋白质、核酸的三维结构 酸和其他分子。原子级结构的可用性， 在了解它们的机制方面取得了进展，并且非常高效 我们开发的计算方法使我们能够 研究受体分子表面的结合部位，并 将配体对接到受体表面，这将在 设计有效的抑制剂。我们最近开发并继续 改进对分子表面的高效描述 成功和高效地用于对接范围广泛的分子 大小从小药物到大分子。使用我们的序列顺序 独立的、基于计算机视觉的方法、内部和表面图案 已被检测到并被编目。使用类似的工具，数据集 制作了蛋白质-蛋白质界面，并用于蛋白质的研究 关联性及其与蛋白质折叠的比较。比较 该数据集与早先生成的蛋白质单体的数据集相比较， 类型之间的异同。 在界面和单链蛋白质中的结构。理论上的 化学方法被结合到分析中，并表明 亲水效应比疏水作用力更重要 接口。一种高效的切割计算算法 蛋白质进入高度疏水、紧凑的亚域模块，用于 创建一个折叠单元数据库，以提供更深入的见解 蛋白质的结构以及它们是如何组装的。 RNA的结构和功能，与蛋白质的结构和功能一样重要 利用基于热力学的算法研究二级结构 以及用于三维预测的分子力学和动力学 模特儿。与诱变实验数据的相关性 和核磁共振显示成功的一致逆转录病毒核糖体移码。 5‘非翻译区(5’URT)的内部核糖体进入，这是一个标志 与保守的、预测的结构相关 元素。在一些细胞的5‘非编码区中预测了类似的元件 对预测方法的改进在不断发展。

The basis of diseases and of their treatments resides in knowledge and comprehension of the three-dimensional structures of proteins, nucleic acids and other molecules. The availability of atomic-level structures, advances made in understanding their mechanisms, and highly efficient computational methodology that we have developed enables us to investigate binding sites on molecular surfaces of receptors, and to dock a ligand unto a receptor surface, which will be useful in the design of potent inhibitors. We have recently developed and continue to improve highly effective descriptions of molecular surfaces that are successfully and efficiently utilized for docking molecules ranging in size from small drugs to macromolecules. Using our sequence-order independent, computer-vision based methods, interior and surface motifs have been detected and catalogued. Using similar tools, a dataset of protein-protein interfaces was made and utilized for studies of protein associations and their comparison to protein folding. Comparisons of this dataset to a dataset of protein monomers, generated earlier, illustrates the similarities and differences between the types of architectures at interfaces and in single-chain proteins. Theoretical chemical methods are incorporated into the analyses and show that hydrophilic effects are more important than hydrophobic forces in interfaces. An efficient computational algorithm designed for cutting proteins into highly hydrophobic, compact, subdomain modules is used to produce a database of folding units that will provide deeper insights into the architecture of proteins and how they are assembled. RNA structure and function, no less important than that of proteins, is studied using thermodynamics-based algorithms for secondary structure and molecular mechanics and dynamics for three-dimensional predictive modelling. Correlations drawn with experimental data from mutagenesis and NMR show successful agreement in retroviral ribosomal frameshifting. Internal ribosome entry in 5' untranslated regions (5' URT), a hallmark of picornaviruses, correlates with conserved, predicted structural elements. Similar elements are predicted in some 5'UTR's of cellular mRNA's. Refinements in predictive methods are continually developed.