Collaborative Research: ABI Development: Algorithms and Software for Discovery of Non-sequential Protein Structure Similarities

伊利诺伊大学芝加哥分校和普林斯顿大学被授予合作补助金，以开发用于比较蛋白质结构的高效和可扩展的计算方法。蛋白质序列和结构正在以越来越快的速度确定。到目前为止，蛋白质数据库中已经有1000多个测序基因组和数千个正在进行中的基因组和50,000多个三维结构。无论是在序列水平上还是在结构水平上考虑蛋白质，比较或比对两个蛋白质都是揭示蛋白质结构、功能和进化规律的基本技术。虽然绝大多数研究工作都集中在序列比较上，但由于蛋白质结构通常比蛋白质序列保存得更好，识别蛋白质之间的结构相似性可以为蛋白质功能提供有价值的线索，并可用于对蛋白质进行分类，分析其进化史，甚至有助于预测蛋白质之间的相互作用。尽管近年来在比较蛋白质结构方面取得了长足的进展，但关键的困难包括检测蛋白质之间共享的、保守的结构，其中单个结构元素在两个序列上的顺序不同。该项目将开发创新方法，以发现与序列顺序无关的亚结构相似性，长期目标是对所有蛋白质结构进行大规模比较。研究团队将制定精确的理论问题，为它们设计高效的算法，并执行和测试得到的算法，以测试准确性和效率问题。用于比较蛋白质结构的最终软件将向科学界发布，预计将对结构生物信息学的进一步研究产生重大和明显的影响。从科学上讲，将开发的亚结构比较方法是通用的，将产生结构蛋白质组学和生物信息学以外的更广泛的影响。例如，拟议项目的生物医学应用在于通过对所有这些亚结构及其潜在序列的系统鉴定来指导蛋白质工程和合理的药物设计。该项目将让本科生和代表不足的少数群体(URM)积极参与研究。其中一个核心部分是吸引城市UIC校区的URM本科生，让他们参与普林斯顿大学的暑期研究，目标是尽可能地招募他们进入普林斯顿大学数量与计算生物学研究生课程。此外，PIS正在规划课程和课程开发、传播研究、指导本科生和研究生、外展和社区参与。项目的结果将通过所有调查人员的网站公布：http://www.cs.uic.edu/~dasgupta http://gila.bioengr.uic.edu/lab http://www.cs.princeton.edu/~mona

The University of Illinois at Chicago and Princeton University are awarded collaborative grants to develop efficient and scalable computational methods for comparing protein structures. Protein sequences and structures are being determined at an increasingly rapid rate. To date, there are more than 1000 sequenced genomes with several thousand more in progress and over 50,000 three-dimensional structures in the Protein Data Bank. Whether considering proteins at the level of sequence or structure, comparing or aligning two proteins is the fundamental technique for uncovering principles of protein structure, function and evolution. While the vast majority of research efforts have focused on sequence comparisons, since protein structures are generally better conserved than protein sequences, identifying structural similarity between proteins can yield valuable clues to protein function and can be used to classify proteins, analyze their evolutionary histories and even to help predict protein interactions. Though considerable advances have been made in recent years in comparing protein structures, key difficulties include detecting shared, conserved structures between proteins where the individual structural elements are in different orderings on the two sequences. This project will develop innovative methods to enable discovery of sequence-order-independent substructure similarity with a long-term goal of doing a large-scale comparison over all protein structures. The research team will formulate precise theoretical problems, design efficient algorithms for them and implement and test the resulting algorithms to test accuracy and efficiency issues. The final software for comparing protein structures will be released to the scientific community and is expected to provide a significant and demonstrable impact on further research in structural bioinformatics.Scientifically, the methodologies to be developed for substructure comparison are general and will have broader impacts beyond structural proteomics and bioinformatics. For example, a biomedical application of the proposed project lies in guiding protein engineering and rational drug design via a systematic identification of all such substructures and their underlying sequences. The project will involve undergraduates and under-represented minority (URM) groups in active research. A central component is to engage URM undergraduate students from the urban UIC campus and involve them in summer research at Princeton with the goal of possible recruitment into Princeton's graduate program in Quantitative and Computational Biology. Additionally, the PIs are planning course and curriculum development, dissemination of research, mentoring of undergraduate and graduate students, outreach and community involvement.The outcomes of the project will be made available through the websites of all the investigators: http://www.cs.uic.edu/~dasgupta http://gila.bioengr.uic.edu/lab http://www.cs.princeton.edu/~mona