Pang Yuan-Ping
Computer-Aided Molecular Design Laboratory, Mayo Clinic, Rochester, MN 55905, USA.
Heliyon. 2016 Sep 20;2(9):e00161. doi: 10.1016/j.heliyon.2016.e00161. eCollection 2016 Sep.
Predicting crystallographic B-factors of a protein from a conventional molecular dynamics simulation is challenging, in part because the B-factors calculated through sampling the atomic positional fluctuations in a picosecond molecular dynamics simulation are unreliable, and the sampling of a longer simulation yields overly large root mean square deviations between calculated and experimental B-factors. This article reports improved B-factor prediction achieved by sampling the atomic positional fluctuations in multiple picosecond molecular dynamics simulations that use uniformly increased atomic masses by 100-fold to increase time resolution. Using the third immunoglobulin-binding domain of protein G, bovine pancreatic trypsin inhibitor, ubiquitin, and lysozyme as model systems, the B-factor root mean square deviations (mean ± standard error) of these proteins were 3.1 ± 0.2-9 ± 1 Å for Cα and 7.3 ± 0.9-9.6 ± 0.2 Å for Cγ, when the sampling was done for each of these proteins over 20 distinct, independent, and 50-picosecond high-mass molecular dynamics simulations with AMBER forcefield FF12MC or FF14SB. These results suggest that sampling the atomic positional fluctuations in multiple picosecond high-mass molecular dynamics simulations may be conducive to prediction of crystallographic B-factors of a folded globular protein.
从传统分子动力学模拟预测蛋白质的晶体学B因子具有挑战性，部分原因在于通过皮秒分子动力学模拟中原子位置涨落采样计算得到的B因子不可靠，而更长模拟的采样会导致计算得到的和实验测得的B因子之间出现过大的均方根偏差。本文报道了通过在多个皮秒分子动力学模拟中采样原子位置涨落实现的改进B因子预测，这些模拟使用均匀增加100倍的原子质量来提高时间分辨率。以蛋白G的第三个免疫球蛋白结合结构域、牛胰蛋白酶抑制剂、泛素和溶菌酶作为模型系统，当对这些蛋白质分别在20个不同、独立且时长为50皮秒的采用AMBER力场FF12MC或FF14SB的高质量分子动力学模拟中进行采样时，这些蛋白质的Cα原子的B因子均方根偏差（均值±标准误差）为3.1±0.2 - 9±1 Å，Cγ原子的为7.3±0.9 - 9.6±0.2 Å。这些结果表明，在多个皮秒高质量分子动力学模拟中采样原子位置涨落可能有助于预测折叠球状蛋白质的晶体学B因子。
