Biomedical subjects

Yong Duan

Publications and source records attributed to Yong Duan.

39 records · Page 3Linked to original sources

PubMed2003

Breaking non-native hydrophobic clusters is the rate-limiting step in the folding of an alanine-based peptide.

The formation mechanism of an alanine-based peptide has been studied by all-atom molecular dynamics simulations with a recently developed all-atom point-charge force field and the Generalize Born continuum solvent model at an effective salt concentration of 0.2M. Thirty-two simulations were conducted. Each simulation was performed for 100 ns. A surprisingly complex folding process was observed. The development of the helical content can be divided into three phases with time constants of 0.06-0.08, 1.4-2.3, and 12-13 ns, respectively. Helices initiate extreme rapidly in the first phase similar to that estimated from explicit solvent simulations. Hydrophobic collapse also takes place in this phase. A folding intermediate state develops in the second phase and is unfolded to allow the peptide to reach the transition state in the third phase. The folding intermediate states are characterized by the two-turn short helices and the transition states are helix-turn-helix motifs-both of which are stabilized by hydrophobic clusters. The equilibrium helical content, calculated by both the main-chain Phi-Psi torsion angles and the main-chain hydrogen bonds, is 64-66%, which is in remarkable agreement with experiments. After corrected for the solvent viscosity effect, an extrapolated folding time of 16-20 ns is obtained that is in qualitative agreement with experiments. Contrary to the prevailing opinion, neither initiation nor growth of the helix is the rate-limiting step. Instead, the rate-limiting step for this peptide is breaking the non-native hydrophobic clusters in order to reach the transition state. The implication to the folding mechanisms of proteins is also discussed.

Alanine↗

PubMed2003

A point-charge force field for molecular mechanics simulations of proteins based on condensed-phase quantum mechanical calculations.

Molecular mechanics models have been applied extensively to study the dynamics of proteins and nucleic acids. Here we report the development of a third-generation point-charge all-atom force field for proteins. Following the earlier approach of Cornell et al., the charge set was obtained by fitting to the electrostatic potentials of dipeptides calculated using B3LYP/cc-pVTZ//HF/6-31G** quantum mechanical methods. The main-chain torsion parameters were obtained by fitting to the energy profiles of Ace-Ala-Nme and Ace-Gly-Nme di-peptides calculated using MP2/cc-pVTZ//HF/6-31G** quantum mechanical methods. All other parameters were taken from the existing AMBER data base. The major departure from previous force fields is that all quantum mechanical calculations were done in the condensed phase with continuum solvent models and an effective dielectric constant of epsilon = 4. We anticipate that this force field parameter set will address certain critical short comings of previous force fields in condensed-phase simulations of proteins. Initial tests on peptides demonstrated a high-degree of similarity between the calculated and the statistically measured Ramanchandran maps for both Ace-Gly-Nme and Ace-Ala-Nme di-peptides. Some highlights of our results include (1) well-preserved balance between the extended and helical region distributions, and (2) favorable type-II poly-proline helical region in agreement with recent experiments. Backward compatibility between the new and Cornell et al. charge sets, as judged by overall agreement between dipole moments, allows a smooth transition to the new force field in the area of ligand-binding calculations. Test simulations on a large set of proteins are also discussed.

Algorithms↗

PubMed2003

[Application of vascular surgery in the treatment of thoracic neoplasm].

OBJECTIVE: To investigate superior vena cava (SVC) and anonymous vein resection with prosthesis replacement for lung carcinoma and mediastinal tumor, and to assess the surgical procedure and prognosis. METHODS: Experimental research: Eighteen adult dogs were divided randomly into two groups. Group A (n = 9) underwent blocking of the SVC system, and Group B (n = 9) underwent SVC resection with prosthesis replacement. The SVC pressure and histological changes of brain tissue were measured and evaluated for group A. The histological changes of prosthesis were studied in group B. Clinical research: Fifty-six patients with thoracic neoplasm were studied, of which 42 were lung carcinoma and 14 were mediastinal tumor. Resection of primary lesions and metastatic lymph nodes with replacement of SVC system were performed for all patients. Long-term follow-up was performed. RESULTS: Experimental research: In Group A, the pressure of SVC was higher when both SVC and the azygous vein were blocked as compared to SVC blocking only (P < 0.05); hyperemia and edema of brain tissue were not observed in two-hour obstruction. The inner face of vascular prosthesis was covered with fibrin two months after operation in group B. Vascular endothelial cells were found to grow in it, and there was no thrombosis without anticoagulation. Clinical research revealed that there was no death associated with the operation and there was no early or late obstruction of SVC. The survival rates of the patients with lung carcinoma in 1, 3 and 5 years were 84.2% 40.9% and 38.9% respectively. The patients with mediastinal tumor were all alive except 1 patient who died of metastasis. CONCLUSIONS: Radical resection combined with prosthesis replacement of SVC system extends the indications of thoracic neoplasm resection and improve the long-term survival rate and living qualities of the patients. It may be recommended in the surgical treatment of thoracic tumor.

Animals↗