2004.09~2008.07
北京大学生命科学学院
本科生
2008.08~2014.12
美国普渡大学化学系
博士生
2015.01~2015.10
美国普渡大学化学系 博士后
2015.11~2019.11
加拿大多伦多大学生物化学系 博士后
2019.12~
至今
北京大学药学院化学生物学系 研究员、博士生导师
研究方向
:
课题组主要研究蛋白质等生物大分子的结构以及微观动态性质,利用核磁共振等实验和计算方法开展药物开发设计相关的各类课题项目。近期研究方向主要包括以下几个方面。
1.
对生物大分子别构调节效应机制的研究。该项研究主要基于目前已知存在别构调节效应的几类蛋白质生物大分子,通过其各个部位的微观动态性质了解别构调节位点与活性作用位点之间的耦合机制,从而对别构调节位点的识别提供直接的实验依据。
2.
与内源无序蛋白相关的药物开发研究。内源无序蛋白在生理条件下缺乏特定的二级结构,难以通过晶体学等实验方法对其进行结构方面的研究。核磁共振实验所测得的微观动态性质是能够从内源无序蛋白所了解到的少数几类性质之一,对于针对内源无序蛋白的药物开发设计具有重要的指导意义。
3.
核磁共振脉冲序列的开发。目前已经存在多种核磁脉冲序列用于各类分子性质的测量,然而很多实验仍然存在灵敏度较低以及虚假信号干扰等问题,因此仍有待于对相关的核磁脉冲序列进行进一步的优化,以及开发新型的核磁脉冲序列等。
发表论文
:
1.
Yuwen T.
, Rui H., Vallurupalli P., Kay L. E., A methyl-TROSY based
1
H relaxation dispersion experiment for studies of conformational exchange in high molecular weight proteins. Angew. Chem. Int. Ed., 2019, 58(19), 6250–6254.
2.
Yuwen T.
, Sekhar A., Baldwin A. J., Vallurupalli P., Kay L. E., Measuring diffusion constants of invisible protein conformers by triple
-
quantum
1
H CPMG relaxation dispersion. Angew. Chem. Int. Ed., 2018, 57(51), 16777–16780.
3.
Yuwen T.
, Bah A., Brady J. P., Ferrage F., Bouvignies G., Kay L. E., Measuring solvent hydrogen exchange rates by multifrequency excitation
15
N CEST: Application to protein phase separation. J. Phys. Chem. B, 2018, 122(49), 11206–11217.
4.
Yuwen T.
, Kay L. E., Bouvignies G., Dramatic decrease in CEST measurement times using multi-site excitation. ChemPhysChem, 2018, 19(14), 1707–1710.
5
.
Yuwen T.
, Bouvignies G., Kay L. E., Exploring methods to expedite the recording of CEST datasets using selective pulse excitation. J. Magn. Reson., 2018, 292, 1–7.
6
.
Yuwen T.
, Brady J. P., Kay L. E., Probing conformational exchange in weakly interacting, slowly exchanging protein systems via off-resonance R
1ρ
experiments: Application to studies of protein phase separation. J. Am. Chem. Soc., 2018, 140(6), 2115–2126.
7
.
Yuwen T.
, Kay L. E., A new class of CEST experiment based on selecting different magnetization components at the start and end of the CEST relaxation element: an application to
1
H CEST. J. Biomol. NMR, 2018, 70(2), 93–102.
8
.
Yuwen T.
, Sekhar A., Kay L. E., Separating dipolar and chemical exchange magnetization transfer processes in
1
H-CEST. Angew. Chem. Int. Ed., 2017, 56(22), 6122–6125.
9
.
Yuwen T.
, Vallurupalli P., Kay L. E., Enhancing the sensitivity of CPMG relaxation dispersion to conformational exchange processes by multiple-quantum spectroscopy. Angew. Chem. Int. Ed., 2016, 55(38), 11490–11494.
10
.
Yuwen T.
, Xue Y., Skrynnikov N. R., Role of electrostatic interactions in binding of peptides and intrinsically disordered proteins to their folded targets: 2. The model of encounter complex involving the double mutant of the c-Crk N-SH3 domain and peptide Sos. Biochemistry, 2016, 55(12), 1784–1800.
欢迎研究生和博士后加入我们!更多信息请参见课题组主页:
http://sklnbd.bjmu.edu.cn/team/yuwentairan/