Theoretical Studies of the Cytosol

乔治敦大学的Toshiko Ichiye获得了CHE分部化学理论、模型和计算方法项目的奖励，他开发了一种新的力场，用于模拟细胞质溶胶水组分中的生物大分子。MCB的生物物理学项目是该提案的共同资助方。正在开发新的参数，用于在细胞质溶胶中发现的水、离子和共溶质，这些参数与现有的生物大分子力场兼容。该力场基于软粘偶极子-四极子-八极子（SSDQO）水模型，该模型再现了一系列温度和压力下液态水的性质，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，其次是其他离子以及细胞中常见的渗透物和代谢物。参数优化是由量子力学计算指导，并通过实验衍射，热力学，介电和动态数据进行验证。计算机硬件的发展使模拟细胞环境中的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生命系统中正常和患病状态下的功能开辟了新的视野。然而，虽然许多工作都集中在发展生物分子本身的模拟，但很少有人关注如何模拟环境，尽管它对这些分子的结构和功能很重要。因此，正在开发一种强大的新力场，用于在细胞质溶胶中发现的组分，以与现有的生物分子力场兼容。力场正在CHARMM中实现，CHARMM是一种广泛使用的生物模拟计算机程序，从而使其广泛应用于科学界。此外，它正在被实施到CHARMM的CHARMMing网络界面的课程计划中，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.