Theoretical Studies of the Cytosol

乔治城大学的Toshiko Ichiye获得了CHE部门化学理论，模型和计算方法计划的奖项，以开发一种新的力场，用于模拟细胞质含水组分中的生物大分子。MCB的生物物理学计划共同资助了这一提议。正在开发新的参数的水，离子，和共溶质中发现的细胞质，是兼容的生物大分子与现有的力场使用。力场是基于软粘性偶极-四极-八极（SSDQO）水模型，该模型再现了液态水在一定温度和压力范围内的性质，但计算效率很高。最初的溶质目标是离子Na+、K+和Cl-以及共溶质三甲胺-N-氧化物和尿素，随后是其他离子以及细胞中通常发现的渗透剂和代谢物。参数优化是由量子力学计算指导和验证实验衍射，热力学，介电和动态数据。计算机硬件的发展使得在细胞环境中模拟蛋白质和核酸等生物大分子成为可能，这为理解它们在真实的生命系统中在正常和患病状态下的功能开辟了新的视野。然而，虽然很多工作都集中在开发生物分子本身的模拟，很少有人注意到如何模拟环境，尽管它的重要性，这些分子的结构和功能。因此，一个强大的新的力场中发现的细胞质中的成分正在开发与现有的生物分子的力场兼容。该力场正在CHARMM中实施，CHARMM是一种广泛使用的生物模拟计算机程序，从而使其广泛适用于科学界。此外，正在将其纳入CHARMM的CHARMMing网络界面的课程计划，从而促进全世界新科学家的教育。

Toshiko Ichiye of Georgetown University is supported by an award from the Chemical Theory, Models and Computational Methods program in the CHE division to develop a new force field for simulations of biological macromolecules in the aqueous component of the cytosol. The Biophysics program in MCB is cofunding this proposal. New parameters are being developed for water, ions, and co-solutes found in the cytosol that are compatible for use with existing force fields for biological macromolecules. The force field is based on the soft sticky dipole-quadrupole-octupole (SSDQO) water model, which reproduces properties of liquid water over a range of temperatures and pressures and yet is computationally efficient. Initial solute targets are the ions Na+, K+, and Cl- and the co-solutes trimethylamine-N-oxide and urea, followed by other ions as well as osmolytes and metabolites typically found in the cell. The parameter optimization is being guided by quantum mechanical calculations and validated against experimental diffraction, thermodynamic, dielectric, and dynamic data. Developments in computer hardware are making possible simulations of biological macromolecules such as proteins and nucleic acids in cellular environments, which opens new horizons for understanding how they function in both normal and diseased states in real living systems. However, while much work has focused on developing the simulations of the biomolecules themselves, little attention has been paid on how to simulate the environment despite its importance for the structure and function of these molecules. Thus, a robust new force field for the components found in the cytosol is being developed to be compatible with existing force fields for the biomolecules. The force field is being implemented into CHARMM, a widely-used computer program for biological simulations, thus making it widely available to the scientific community. In addition, it is being implemented into lesson plans for the CHARMMing web-interface for CHARMM, thus promoting the education of new scientists throughout the world.