Career: Probabilistic Methods and Algorithms to Solve Protein Folding Problems

该项目属于计算分子生物学领域；具体来说，它解决了蛋白质折叠和病毒外壳自组装的问题。与蛋白质折叠相关的“重大挑战”问题是，当只给定蛋白质的氨基酸序列时，确定蛋白质如何在三维空间中折叠。解决蛋白质折叠问题的重要第一步是解决基序识别问题（即给定已知的3D结构或基序，确定该基序是否发生在未知的氨基酸序列中）。这项工作的目标是开发新的算法，仅基于正确的成对相关概率，它优于现有的基序识别算法。正在编写这些算法的实现程序。事实上，该包裹正在帮助发现诸如Mollney鼠白血病、流感血凝素和HIV等病毒中的盘绕线圈基序。螺旋基序被认为是蛋白质与细胞膜融合或结合的机制。这项持续的研究涉及在可用数据较少的情况下识别基序，预测基序的链间相互作用，以及发现蛋白质三维结构的新见解。该项目的第二部分涉及研究病毒外壳的自组装。特别是，通过计算模拟这些外壳是如何形成的，有希望提出干扰这些病毒生长和导致它们畸形的方法。本职业补助金的教育部分包括：(a)开发跨学科（计算机科学、数学和生物学）本科和研究生课程，以及计算分子生物学、离散数学和（生物）算法理论课程；(b)发展计算分子生物学的本科生和研究生研讨会。本科生参与开发扩展系统项目和病毒外壳组装项目。（这是美国国家科学基金会本科生研究经验项目和麻省理工学院本科生研究机会项目的一部分。）

The project is in the area of computational molecular biology; specifically it addresses problems in protein folding and the self-assembly of virus shells. The `grand challenge` problem associated with protein folding is to determine how a protein will fold in 3-dimensions when given only its amino acid sequence. An important first step in tackling the protein folding problem is a solution to the motif recognition problem (i.e., given a known 3D structure, or motif, determining whether this motif occurs in an unknown amino acid sequence). The goal of this effort is to develop new algorithms, based solely on the right pairwise correlation probabilities, which out perform existing motif recognition algorithms. An implementation of these algorithms, is being programmed. In fact, the package is aiding in the discovery of the coiled-coil motif in such viruses as Mollney murine leukemia, influenza hemagglutinin, and HIV. The coiled-coil motif is thought to be the mechanism by which proteins fuse with or bind to the cell membrane. This continuing research deals with recognizing motifs when less data is available, predicting inter-strand interactions in motifs, and finding new insights into the 3-dimensional structure of proteins. The second part of the project involves studying the self-assembly of virus shells. In particular, by computationally modeling how these shells are built, it is hopefully possible to suggest ways of interfering with the growth of these viruses and of causing their deformity. The Educational Component of this CAREER Grant includes: (a) Development of interdisciplinary (computer science, mathematics, and biology) undergraduate and graduate courses and curriculum in computational molecular biology, discrete mathematics and the theory of (biological) algorithms; (b) Development of both undergraduate and graduate seminars in computational molecular biology. Participation of undergraduate students in developing the extended system project and the Virus Shell Assembly project. (This is part of the Research Experiences for Undergraduates Program at NSF and Undergraduate Research Opportunities Program of MIT.)