Biomedical subjects

Yongjin Zhu

Publications and source records attributed to Yongjin Zhu.

3 recordsLinked to original sources

PubMed2004

Understanding the key factors that control the rate of beta-hairpin folding.

Both turn sequence and interstrand hydrophobic side-chain-side-chain interaction have been suggested to be important determinants of beta-hairpin stability. However, their roles in controlling the folding dynamics of beta-hairpins have not been clearly determined. Herein, we investigated the structural stability and folding kinetics of a series of tryptophan zippers by static IR and CD spectroscopies and the IR temperature jump method. Our results support a beta-hairpin folding mechanism wherein the rate-limiting event corresponds to the formation of the turn. We find that the logarithm of the folding rate depends linearly on the entropic change associated with the turn formation, where faster folding correlates with lower entropic cost. Moreover, a stronger turn-promoting sequence increases the stability of a beta-hairpin primarily by increasing its folding rate, whereas a stronger hydrophobic cluster increases the stability of a beta-hairpin primarily by decreasing its unfolding rate.

Amino Acid Sequence↗

PubMed2003

Ultrafast folding of alpha3D: a de novo designed three-helix bundle protein.

Here, we describe the folding/unfolding kinetics of alpha3D, a small designed three-helix bundle. Both IR temperature jump and ultrafast fluorescence mixing methods reveal a single-exponential process consistent with a minimal folding time of 3.2 +/- 1.2 micros (at approximately 50 degrees C), indicating that a protein can fold on the 1- to 5-micros time scale. Furthermore, the single-exponential nature of the relaxation indicates that the prefactor for transition state (TS)-folding models is probably >or=1 (micros)-1 for a protein of this size and topology. Molecular dynamics simulations and IR spectroscopy provide a molecular rationale for the rapid, single-exponential folding of this protein. alpha3D shows a significant bias toward local helical structure in the thermally denatured state. The molecular dynamics-simulated TS ensemble is highly heterogeneous and dynamic, allowing access to the TS via multiple pathways.

Kinetics↗

PubMed2002

Helix formation via conformation diffusion search.

The helix-coil transition kinetics of an alpha-helical peptide were investigated by time-resolved infrared spectroscopy coupled with laser-induced temperature-jump initiation method. Specific isotope labeling of the amide carbonyl groups with 13C at selected residues was used to obtain site-specific information. The relaxation kinetics following a temperature jump, obtained by probing the amide I' band of the peptide backbone, exhibit nonexponential behavior and are sensitive to both initial and final temperatures. These data are consistent with a conformation diffusion process on the folding energy landscape, in accord with a recent molecular dynamics simulation study.

Computer Simulation↗