CAREER: Novel Sampling Approaches for Protein Modeling Applications

职业：蛋白质建模应用的新采样方法李耀航北卡罗来纳A&T州立大学准确建模蛋白质或蛋白质复杂结构被认为是一项具有广泛经济和科学影响的重大挑战。关键的障碍之一是缺乏可靠的采样方法来有效地探索极大的蛋白质构象空间。这个职业项目研究高效的采样方法，能够以目前计算蛋白质建模所不能达到的精度和可靠性来预测高分辨率蛋白质结构。其基本原理是通过多评分函数采样来整合各种基于物理和知识的评分函数，以探索复杂的蛋白质构象空间。研究工作包括：1)在蛋白质结构建模中建立具有理论和数学严密性的多评分函数采样计算模型；2)设计新的采样算法以有效地探索大的蛋白质构象空间；3)将采样算法应用于蛋白质从头算折叠和蛋白质-蛋白质对接等重要的蛋白质建模应用；4)开发资源高效的蛋白质建模编程范例。本研究开发的高效采样方法可应用于各种重要的计算生物学应用，这将为实际应用提供可靠的提高蛋白质模型分辨率的踏脚石。高分辨率蛋白质建模的成功将对基因组研究、疾病研究、生物能源开发和药物设计行业产生重大影响。除了它的研究影响，这个职业项目的教育目标是吸引优秀的学生，特别是少数族裔，参与计算生物学研究和从事计算科学事业。

CAREER: Novel Sampling Approaches for Protein Modeling ApplicationsYaohang LiNorth Carolina A&T State UniversityAccurately modeling protein or protein complex structure is considered a significant grand challenge that has broad economic and scientific impact. One of the key obstacles is the absence of a reliable sampling method that can efficiently explore the tremendously large protein conformation space. This CAREER project investigates efficient sampling approaches that can lead to prediction of high resolution protein structures with accuracy and reliability currently not achievable in computational protein modeling. The rationale is to integrate various physics- and knowledge-based scoring functions via multi-scoring functions sampling to explore the complex protein conformation space. The research work includes 1) establishing computational models for multi-scoring functions sampling in protein structure modeling with theoretically and mathematically rigorous justification; 2) designing novel sampling algorithms to efficiently explore large protein conformation space; 3) applying the sampling algorithms to important protein modeling applications including ab initio protein folding and protein-protein docking; and 4) developing a resource-efficient protein modeling programming paradigm.The efficient sampling approaches developed in this research can be applied to a variety of important computational biology applications, which will provide a critical stepping stone toward reliable resolution improvement in protein models for practical use. Success of high resolution protein modeling will have significant impact on genomic study, disease research, bio-energy development, and the drug-design industry. In addition to its research impact, the educational goal of this CAREER project is to attract excellent students, particularly the minorities, to participate in computational biology research and pursue computational science career.