Steinbrecher T, Latzer J, Case D A
Institute for Physical Chemistry, Kaiserstr 12, University Karlsruhe, KIT, 76131 Karlsruhe, Germany, and Dept. of Chemistry and Chemical Biology, and BioMaPS Institute, 174 Frelinghuysen Road, Rutgers University, Piscataway, NJ 08854.
J Chem Theory Comput. 2012 Nov 13;8(11):4405-4412. doi: 10.1021/ct300613v. Epub 2012 Sep 12.
We report AMBER force field parameters for biological simulations involving phosphorylation of serine, threonine or tyrosine. The initial parameters used RESP fitting for the atomic partial charges and standard values for all other parameters such as Lennard-Jones coefficients. These were refined with the aid of a thermodynamic cycle consisting of experimentally determined pKa values, solvation energies from molecular dynamics free energy simulations, and gas phase basicities from QM calculations. A polarization energy term was included to account for the charge density change between the gas-phase and solution, and solvation free energies were determined using thermodynamic integration. Parameter adjustment is required to obtain consistent thermodynamic results with better balanced electrostatic interactions between water and the phosphate oxygens. To achieve this we modified the phosphate oxygen radii. A thermodynamically consistent parameter set can be derived for monoanions and requires an increase of the van der Waals phosphate oxygen radii of approximately 0.09 Å. Larger, residue-specific radii appear to be needed for dianions. The revised parameters developed here should be of particular interest for environments where simulations of multiple protonation states may be of interest.
我们报告了用于涉及丝氨酸、苏氨酸或酪氨酸磷酸化的生物模拟的AMBER力场参数。初始参数使用RESP拟合原子部分电荷，并采用所有其他参数的标准值，如 Lennard-Jones 系数。这些参数借助一个热力学循环进行了优化，该循环由实验测定的pKa值、分子动力学自由能模拟得到的溶剂化能以及量子力学计算得到的气相碱度组成。引入了一个极化能项来解释气相和溶液之间的电荷密度变化，并使用热力学积分确定溶剂化自由能。需要调整参数以获得一致的热力学结果，并使水与磷酸根氧之间的静电相互作用达到更好的平衡。为此，我们修改了磷酸根氧的半径。对于单阴离子，可以推导出一个热力学一致的参数集，这需要将范德华磷酸根氧半径增加约0.09 Å。对于双阴离子，似乎需要更大的、特定残基的半径。这里开发的修订参数对于可能需要模拟多个质子化状态的环境应该特别有用。
