Biomedical subjects

Sheh-Yi Sheu

Publications and source records attributed to Sheh-Yi Sheu.

4 recordsLinked to original sources

PubMed2006

Selectivity principle of the ligand escape process from a two-gate tunnel in myoglobin: molecular dynamics simulation.

We proposed a selectivity principle for the ligand escape process from two fluctuating bottlenecks in a cavity with a multigate inside a myoglobin pocket. Our previous analytical theory proposed a fluctuating bottleneck model for a Brownian particle passing through two gates on a cavity surface of an enzyme protein and has determined the escape rate in terms of the time-dependent gate function and the competition effect. It illustrated that with two (or more than two) gates on a cavity surface the gate modulation, which is controlled by protein fluctuation, dominates the ligand escape pathway. We have performed a molecular dynamics simulation to investigate the selectivity principle of the ligand escape process from two-gate tunnel in myoglobin. The simulation results confirm our theoretical conjecture. It indicates that the escape process is actually entropy driven, and the ligand escape pathway is chosen via the gate modulation. This suggests an interesting intrinsic property, that is, the oxymyoglobin tertiary structure is favorable to the departure of the ligand from one direction rather than through a biased random walk.

Computer Simulation↗

PubMed2005

Molecular dynamics simulation of entropy driven ligand escape process in heme pocket.

Molecular dynamics simulations were performed to investigate the gate effect of protein motion on the escape of O(2) from the heme pocket. The existing geometric entropy in a spherical cavity pushes the ligand toward the cavity surface, and then the ligand escape along the cavity surface is controlled by the gate size and gate modulation, i.e., protein dynamics regulate the gating behavior, which is an inherent feature of proteins such as myoglobin. Our simulation results confirm that the ligand escape process is basically entropy driven.

Journal Article↗

PubMed2004

Structural variation in human apolipoprotein E3 and E4: secondary structure, tertiary structure, and size distribution.

Human apolipoprotein E (apoE) is a 299-amino-acid protein with a molecular weight of 34 kDa. The difference between the apoE3 and apoE4 isoforms is a single residue substitution involving a Cys-Arg replacement at residue 112. ApoE4 is positively associated with atherosclerosis and late-onset and sporadic Alzheimer's disease (AD). ApoE4 and its C-terminal truncated fragments have been found in the senile plaques and neurofibrillary tangles in the brain of AD patients. However, detail structural information regarding isoform and domain interaction remains poorly understood. We prepared full-length, N-, and C-terminal truncated apoE3 and apoE4 proteins and studied their structural variation. Sedimentation velocity and continuous size distribution analysis using analytical ultracentrifugation revealed apoE3(72-299) as consisting of a major species with a sedimentation coefficient of 5.9. ApoE4(72-299) showed a wider and more complicated species distribution. Both apoE3 and E4 N-terminal domain (1-191) existed with monomers as the major component together with some tetramer. The oligomerization and aggregation of apoE protein increased when the C-terminal domain (192-271) was incorporated. The structural influence of the C-terminal domain on apoE is to assist self-association with no significant isoform preference. Circular dichroism and fluorescence studies demonstrated that apoE4(72-299) possessed a more alpha-helical structure with more hydrophobic residue exposure. The structural variation of the N-terminal truncated apoE3 and apoE4 protein provides useful information that helps to explain the greater aggregation of the apoE4 isoform and thus has implication for the involvement of apoE4 in AD.

Alleles↗

PubMed2003

Energetics of hydrogen bonds in peptides.

Hydrogen bonds and their relative strengths in proteins are of importance for understanding protein structure and protein motions. The correct strength of such hydrogen bonds is experimentally known to vary greatly from approximately 5-6 kcal/mol for the isolated bond to approximately 0.5-1.5 kcal/mol for proteins in solution. To estimate these bond strengths, here we suggest a direct novel kinetic procedure. This analyzes the timing of the trajectories of a properly averaged dynamic ensemble. Here we study the observed rupture of these hydrogen bonds in a molecular dynamics calculation as an alternative to using thermodynamics. This calculation is performed for the isolated system and contrasted with results for water. We find that the activation energy for the rupture of the hydrogen bond in a beta-sheet under isolated conditions is 4.76 kcal/mol, and the activation energy is 1.58 kcal/mol for the same beta-sheet in water. These results are in excellent agreement with observations and suggest that such a direct calculation can be useful for the prediction of hydrogen bond strengths in various environments of interest.

Calorimetry↗