STEERED MOLECULAR DYNAMICS-INVESTIGATE PROTEIN FUNCTION

机械蛋白质的折叠/解折叠， 非共价连接的生物分子和生物选择性 跨膜离子通道是许多重要过程的核心， 肌肉拉伸，免疫反应，电信号，是目标， 实验和理论研究。 Schulten博士建议使用 转向分子动力学（SMD）模拟，一种允许人们 研究在实验中不容易检测到的过程，以：1） 了解免疫球蛋白（IG）中夹心结构域的结构 肌联蛋白和纤连蛋白III型（FnIII）结构域已经被自然界设计成 蛋白质可以承受高的力量，并作为压力传感器，并解决 在原子水平上，蛋白质结构域的机械拉伸和展开 通过IG和FnIII结构域的强制解折叠; 2）定量 与抗体成熟相关的蛋白质柔性，并研究半抗原 与结合口袋的残基的相互作用，通过诱导 半抗原; 3）确定平均力的潜力，并解释 K+通道区分K+和Na+离子的保真度， 并且对于在K+通道的签名序列中编码的选择性， 模拟K+离子通过通道。 这些研究将 提供可以直接与实验数据进行比较的结果，以及 通过这些过程的原子级细节来补充观察结果 解释数据。

Folding/unfolding of mechanical proteins, binding/unbinding of non-covalently attached biomolecules, and selectivity of biological transmembrane ion channels are at the heart of many important processes like muscle stretching, immune response, electrical signaling, and are the target of experimental and theoretical investigations. Dr. Schulten proposes to use Steered Molecular Dynamics (SMD) simulations, a tool that allows one to investigate processes which cannot be easily detected in experiments, to: 1) understand how the architecture of sandwich domains in the immunoglobulin (Ig) and fibronectin type III (FnIII) domains of titin has served nature to design proteins which can withstand high forces and act as stress sensors, and resolve at the atomic level the mechanical stretching and unfolding of protein domains by forced unfolding of the Ig and FnIII domains; 2) quantify changes in the protein flexibility connected with antibody maturation and investigate hapten interactions with residues of the binding pocket by inducing the unbinding of the hapten; 3) determine the potential of mean force and explain the basis for the fidelity with which the K+ channel distinguishes between K+ and Na+ ions, and for the selectivity encoded in the signature sequence of the K+ channel by simulating the passing of K+ ions through the channel. These studies will provide results that can be directly compared to experimental data, as well as complement observations through atomic-level details of these processes explaining the data.