生物大分子结构模拟.ppt

生物大分子结构模拟Introduction to Molecular Modeling 王适群 医学生物结构中心 2010.11.22 分子模拟定义 Molecular modeling is the application of computational structural biology to the challenge of biomolecular structure prediction. Its aim is to determine the three-dimensional structure from their sequences. 主要内容 第一部分 蛋 白 分 子 结 构 模 拟 第二部分 核 酸 分 子 结 构 模 拟 蛋 白 分 子 结 构 模 拟 蛋白质的三级结构 (tertiary structure) 结构域(domain)在空间上相对独立 Principles of Protein Structure The Levinthal paradox X-ray crystallography Obtain an ordered protein crystal. Check x-ray diffraction. X-ray crystallography 3. Analyze diffraction pattern and produce an electron density map. 4.Thread the known protein sequence into the density map. X-ray crystallography The molecules must be very pure in order to produce perfect and stable crystals. The method is time-consuming and difficult. （二）核磁共振（nuclear magnetic resonance,NMR） 核磁共振技术可以直接研究溶液和活细胞中相对分子质量较小(20，000 道尔顿以下)的蛋白质、核酸以及其它分子的结构， 这更接近于蛋白质在生物细胞中的自然状态。 此外，通过改变溶液的性质，还可以模拟出生物细胞内的各种生理条件，即蛋白质分子所处的各种环境，以观察这些周围环境的变化对蛋白质分子空间结构的影响。，因此,NMR方法为蛋白质与蛋白质、蛋白质与底物或小分子的相互作用提供了一个有效的观察手段。 NMR - Nuclear Magnetic Resonance A sample is immersed in a magnetic field and bombarded with radio waves. The molecule’s nucleus resonate (spin). This motion is determined and is specific for each molecule type. Principles of NMR NMR - Nuclear MagneticResonance The NMR technique is very time consuming and expensive, and the sample has to be in a concentrated solution, and is limited to small and soluble molecules. PDB: Protein Data Bank Holds 3D models of biological macromolecules (protein, RNA, DNA). All data are available to the public. Obtained by X-Ray crystallography (84%) or NMR spectroscopy (16%). Submitted by biologists and biochemists from around the world. PDB – Protein Data Bank Molecular Modeling DataBase 蛋白结构预测方法 通过同源序列分析或者模式匹配预测蛋白质的空间结构或者结构单元（如锌指结构、螺旋-转角-螺旋结构、DNA结合区域等）。 注意 同源模