基于正弦高斯调制和样条插值的CTF校正模型

Contrast Transfer Function Correction Model Based on Sine and Gaussian Modulation and Spline Interpolation

在基于冷冻电镜的单颗粒三维重构过程中,衬度传递函数(contrast transfer function,CTF)校正是获取高分辨分子结构的关键操作.但传统CTF校正模型存在低频、高频阶段校正值过小、插值方法过于简单等问题,从而降低了重构精度.针对这两个问题,提出了一种新的CTF校正模型.首先,在CTF曲线的低频、高频阶段分别进行正弦和高斯调制,改善了CTF曲线的形态;然后,采用3次样条插值计算非整数傅里叶半径处的CTF值,提高了数据获取的精度,进而提高了重构结果的分辨率.对HBV分子图像进行重构实验,结果表明,使用本模型可以得到更清晰的结构特征,其重构结果分辨率为7.8,高于传统CTF校正重构结果的分辨率8.06.

In the course of 3D reconstruction for protein molecules based on single-particle cryoelectron microscopy, CTF correction has played an important role on obtaining the high resolution molecular structure. However, the traditional CTF correction model has some problems. Firstly, the reconstruction result would be amplified incorrectly in low frequency and instable in high frequency, because CTF value is very small in the two frequency regions. Secondly, the linear interpolation would affect the precision of adjusted data, because it could not match the sinusoidal shape of CTF curve. Thus, the above two issues are studied and a new CTF correction model is proposed. On the one hand, the sine and Gaussian modulation are applied in the low-frequency and high-frequency phase of CTF curve respectively. Thus, the shape of CTF curve is enhanced. On the other hand, the cubic spline interpolation is used for computing the CTF value in the fractional Fourier radius. The accuracy of the data acquisition is improved subsequently. Thereby, the resolution of reconstruction molecular structure is increased. Finally, the reconstruction experiment is carried out with the cryo-EM images of HBV. The experimental results indicate that the structure from our model has more detailed feature than the one from the old model. The resolution of reconstructed strcuture with our method is 7.8 angstrom, which is better than 8.06 angstrom of the one with traditional CTF model.