ALGORITHMS FOR MOLECULAR KINETICS

描述(改编自调查员的申请)：了解 生物分子的动力学是当代科学的一个主要目标 生物学的进步已经朝着单细胞分析的方向发展 利用膜片钳记录、激光陷阱和原子力的分子 显微镜。单分子的研究提供了这样的机会 直接测量分子速率常数以及输出 属性，如电流、位移或力。结合了 能够很容易地使用定点定向来改变分子结构 诱变，分子动力学的分析提供了无与伦比的 对分子结构和功能的洞察很难 通过其他方法获得。单通道电流的分析 拥有最广泛的单分子动力学技术历史。 虽然每年大约有5000篇论文出现在离子频道上， 几乎没有人使用包含在 数据。大多数处理的是平均属性，例如 开阔的或平均的水流。缺乏详细信息的一个主要原因 分析是解逆问题的难点--从 数据添加到模型中。大多数生物学家并不具备 数学能力和那些有能力的人很少尝试这样做 分析因为所需的时间，很难检查 对备选模型的结果和建立的难度 误差限制。这项提议的目标是扩展现有的算法 并开发出用户友好的软件，作为一个“动力学” 随机分子数据的计算器；软件可以快速和 轻松解决逆问题(在某种程度上，此类问题 可逆)。该软件不会要求用户 精通数学或对算法了如指掌。海流 软件同时使用命令行和Motif在Unix环境中运行 图形界面。各种算法提供了优化和 分段。该软件将使用改进后的软件进行统一和扩展 并移植到更常见的IBM/PC，也许还有MacIntosh环境。 该项目的成功预计将导致建立一个 支持随机分子分析的国家用户设备 运动学。

DESCRIPTION (Adapted from the investigator's application): Understanding the dynamics of biological molecules is a major goal of contemporary biology and progress has been in the direction of analysis of single molecules utilizing patch clamp recording, laser traps and atomic force microscopy. The study of single molecules provides the opportunity to directly measure molecular rate constants as well as the output properties such as current, displacement or force. Combined with the ability to readily alter molecular structure using site directed mutagenesis, the analysis of molecular kinetics provides unparalleled insights into molecular structure and function that are difficult to obtain by other methods. The analysis of currents from single channels has the most extensive history of single molecule kinetic techniques. While there are about 5,000 papers per year appearing on ion channels, almost none utilize the vast array of kinetic information contained in the data. Most deal with average properties such as the probability of being open or the mean current. A major reason for the lack of detailed analyses is the difficulty of solving the inverse problem -- going from data to the model. Most biologists do not posses the requisite mathematical skills and those with the skills rarely attempt such analyses because of the time required, the difficulty of checking the results against alternative models and the difficulty of establishing error limits. the goal of this proposal is to extend current algorithms and to develop user friendly software that can serve as a "kinetics calculator" for stochastic molecular data; software that can quickly and easily solve the inverse problem (to the extent that such problems are invertible). The software will not require the user to be mathematically adept or knowledgeable about algorithms. The current software runs in UNIX environment utilizing both command line and Motif graphical interfaces. A variety of algorithms provide optimization and segmentation. This software will be unified and extended using improved and ported to the more common IBM/PC and perhaps MacIntosh environments. Success of this project is expected to lead to establishment of a national user facility supporting the analysis of stochastic molecular kinetics.