STEERED MOLECULAR DYNAMICS-INVESTIGATE PROTEIN FUNCTION

机械蛋白的折叠/去折叠，结合/去结合 非共价连接的生物分子和生物的选择性 跨膜离子通道是许多重要过程的核心，如 肌肉拉伸、免疫反应、电信号和是 实验和理论研究。舒尔滕博士建议使用 转向分子动力学(SMD)模拟，这是一种允许人们 调查在实验中不易检测到的过程，以：1) 了解免疫球蛋白(Ig)中三明治结构域的结构 而Titin的纤维连接蛋白III型(FnIII)结构域已服务于自然设计 能够承受高力并充当应力传感器的蛋白质，并可分解 在原子水平上蛋白质结构域的机械伸展和展开 通过强制展开Ig和FnIII结构域；2)量化 蛋白质柔韧性与抗体成熟及半抗原研究 通过诱导解离与结合袋的残基相互作用 半抗原；3)确定平均力的势，并解释 K+通道区分K+和Na+离子的保真度， 以及对于在K+通道的签名序列中编码的选择性 模拟K+离子通过通道的过程。这些研究将 提供可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.