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Fangqiang Zhu

Publications and source records attributed to Fangqiang Zhu.

9 recordsLinked to original sources
PubMed2006

Charge delocalization in proton channels, I: the aquaporin channels and proton blockage.

The explicit contribution to the free energy barrier and proton conductance from the delocalized nature of the excess proton is examined in aquaporin channels using an accurate all-atom molecular dynamics computer simulation model. In particular, the channel permeation free energy profiles are calculated and compared for both a delocalized (fully Grotthuss shuttling) proton and a classical (nonshuttling) hydronium ion along two aquaporin channels, Aqp1 and GlpF. To elucidate the effects of the bipolar field thought to arise from two alpha-helical macrodipoles on proton blockage, free energy profiles were also calculated for computational mutants of the two channels where the bipolar field was eliminated by artificially discharging the backbone atoms. Comparison of the free energy profiles between the proton and hydronium cases indicates that the magnitude of the free energy barrier and position of the barrier peak for the fully delocalized and shuttling proton are somewhat different from the case of the (localized) classical hydronium. The proton conductance through the two aquaporin channels is also estimated using Poisson-Nernst-Planck theory for both the Grotthuss shuttling excess proton and the classical hydronium cation.

Aquaporin 1↗
PubMed2006

A distance geometry heuristic for expanding the range of geometries sampled during conformational search.

A recent study of crystal structures of protein-ligand complexes has shown that bioactive conformations tend to be more extended than random ones (Diller and Merz, J. Comput. Aid. Mol. Des. 2002, 16, 105-112). Existing conformational sampling techniques produce molecular conformations with a distribution of geometric sizes that may not cover that of the bioactive conformations. Here, we describe a simple heuristic for biasing the conformational search toward more extended or compact conformations, while maintaining excellent sampling. The method uses a boosting strategy to generate a series of conformations, each of which is at least as extended (or compact) as the previous one. We demonstrate that this method significantly expands the range of geometric sizes generated during the search and thus increases the efficiency of sampling bioactive conformations.

Algorithms↗
PubMed2004

Collective diffusion model for water permeation through microscopic channels.

Water permeation through nanometric channels, generally a coupled many-body process, is described in this study by a single collective coordinate. A collective diffusion model is proposed in which water movement at equilibrium is characterized as an unbiased diffusion along this coordinate and water transport in the presence of a chemical potential difference is described as one-dimensional diffusion in a linear potential. The model allows one to determine the osmotic permeability of a water channel from equilibrium simulations.

Aquaporins↗
PubMed2004

Theory and simulation of water permeation in aquaporin-1.

We discuss the difference between osmotic permeability pf and diffusion permeability pd of single-file water channels and demonstrate that the pf/pd ratio corresponds to the number of effective steps a water molecule needs to take to permeate a channel. While pd can be directly obtained from equilibrium molecular dynamics simulations, pf can be best determined from simulations in which a chemical potential difference of water has been established on the two sides of the channel. In light of this, we suggest a method to induce in molecular dynamics simulations a hydrostatic pressure difference across the membrane, from which pf can be measured. Simulations using this method are performed on aquaporin-1 channels in a lipid bilayer, resulting in a calculated pf of 7.1 x 10(-14) cm(3)/s, which is in close agreement with observation. Using a previously determined pd value, we conclude that pf/pd for aquaporin-1 measures approximately 12. This number is explained in terms of channel architecture and conduction mechanism.

Aquaporin 1↗
PubMed2003

Water and proton conduction through carbon nanotubes as models for biological channels.

Carbon nanotubes, unmodified (pristine) and modified through charged atoms, were simulated in water, and their water conduction rates determined. The conducted water inside the nanotubes was found to exhibit a strong ordering of its dipole moments. In pristine nanotubes the water dipoles adopt a single orientation along the tube axis with a low flipping rate between the two possible alignments. Modification can induce in nanotubes a bipolar ordering as previously observed in biological water channels. Network thermodynamics was applied to investigate proton conduction through the nanotubes.

Biomimetic Materials↗
PubMed2003

Retroperitoneoscopic renal pedicle lymphatic disconnection for chyluria.

OBJECTIVE: To report our experiences in retroperitoneoscopic renal pedicle lymphatic stripping for chyluria. METHODS: Six cases of filarial chyluria were admitted to our hospital from November 2001 to June 2002. Of these cases, 4 were men and 2 women, with age ranging from 34 to 52 years (mean, 42 years). Diagnosis was made by using urine test for the presence of chyle and fat globule, cystoscopy, excretory urogram and retrograde pyelography. Chyluria was found on the left renal unit in 2 cases and on the right side in 4 cases. The technique of retroperitoneoscopic management of chyluria consisted of nephrolympholysis, hilar vessel stripping and ureterolympholysis. RESULTS: Operative time ranged from 69 to 120 minutes (mean, 95 minutes). Intraoperative blood loss was 50-180 ml (mean, 85 ml). Chyluria disappeared in all patients immediately after operation. Mild hematuria occurred in 4 cases within 12 hours and disappeared at 24 hours. Subcutaneous emphysema around the lesions was found in 2 cases and was spontaneously absorbed 3 days after the treatment. There was no lymphatic leak at the lesions. The patients were discharged from the hospital 5-9 days after the treatment. All patients gained weight and their haemoglobin and serum protein increased by 13.5 g/L and 3.66 g/L respectively. No chyluria recurrence was reported during 1-1.6 years follow-up. CONCLUSIONS: Retroperitoneoscopic renal pedicle lymphatic disconnection for chyluria is a safe, effective and efficient surgical procedure with minimal invasion, less pain, lower morbidity, short hospital stay and rapid recovery.

Adult↗
PubMed2002

Pressure-induced water transport in membrane channels studied by molecular dynamics.

A method is proposed to measure the water permeability of membrane channels by means of molecular dynamics simulations. By applying a constant force to the bulk water molecules and a counter force on the complementary system, a hydrostatic pressure difference across the membrane can be established, producing a net directional water flow. The hydraulic or osmotic permeability can then be determined by the ratio of the water flux and the pressure difference. The method is applied and tested on an aquaglyceroporin channel through a series of simulations totaling 5 ns in duration.

Aquaporins↗