PubMed Health⌕ Search

Biomedical subjects

Alexander M Smondyrev

Publications and source records attributed to Alexander M Smondyrev.

6 recordsLinked to original sources
PubMed2006

PHASE: a new engine for pharmacophore perception, 3D QSAR model development, and 3D database screening: 1. Methodology and preliminary results.

We introduce PHASE, a highly flexible system for common pharmacophore identification and assessment, 3D QSAR model development, and 3D database creation and searching. The primary workflows and tasks supported by PHASE are described, and details of the underlying scientific methodologies are provided. Using results from previously published investigations, PHASE is compared directly to other ligand-based software for its ability to identify target pharmacophores, rationalize structure-activity data, and predict activities of external compounds.

Computer Simulation↗
PubMed2002

Molecular dynamics simulation of proton transport through the influenza A virus M2 channel.

The structural and dynamical properties of a solvated proton in the influenza A virus M2 channel are studied using a molecular dynamics (MD) simulation technique. The second-generation multi-state empirical valence bond (MS-EVB2) model was used to describe the interaction between the excess proton and the channel environment. Solvation structures of the excess proton and its mobility characteristics along the channel were determined. It was found that the excess proton is capable of crossing the channel gate formed by the ring of four histidine residues even though the gate was only partially open. Although the hydronium ion itself did not cross the channel gate by traditional diffusion, the excess proton was able to transport through the ring of histidine residues by hopping between two water molecules located at the opposite sides of the gate. Our data also indicate that the proton diffusion through the channel may be correlated with the changes in channel conformations. To validate this observation, a separate simulation of the proton in a "frozen" channel has been conducted, which showed that the proton mobility becomes inhibited.

Biological Transport↗
PubMed2002

Interfacing molecular dynamics and macro-scale simulations for lipid bilayer vesicles.

A continuum-level model for a giant unilamellar vesicle (GUV) is bridged to a corresponding atomistic model of a dimyristoylphosphatidylcholine (DMPC) bilayer at various cholesterol concentrations via computation of the bulk modulus. The bulk modulus and other microscopically determined parameters are passed to a continuum-level model operating in time- and length-scales orders of magnitude beyond that which is accessible by atomistic-level simulation. The continuum-level simulation method used is the material point method (MPM), and the particular variation used here takes advantage of the spherical nature of many GUVs. An osmotic pressure gradient due to a solvent concentration change is incorporated into the continuum-level simulation, resulting in osmotic swelling of the vesicle. The model is then extended to treat mixtures of DMPC and cholesterol, where small domains of different composition are considered.

Algorithms↗
PubMed2002

Calculating the bulk modulus for a lipid bilayer with nonequilibrium molecular dynamics simulation.

Nonequilibrium molecular dynamics (NEMD) computer simulations are used to calculated the bulk modulus for a dimyristoylphosphatidylcholine bilayer. A methodology is developed whereby NEMD can be effectively used to calculate material properties for complex systems that undergo long time-scale conformational changes. It is found that the bulk modulus upon expansion from a zero stress state agrees well with experimental estimates. However, it is also found that the modulus upon contraction from a zero stress state is larger. From a molecular perspective, it is possible to explain this phenomena by examining the molecular origins of the pressure response. The finding that the two moduli are not equal upon compression and expansion is in apparent contradiction to osmotic stress experiments where the area modulus was found to be the same upon expansion and contraction. This issue is addressed.

Algorithms↗
PubMed2002

Molecular dynamics simulation of proton transport near the surface of a phospholipid membrane.

The structural and dynamical properties of a hydrated proton near the surface of DMPC membrane were studied using a molecular dynamics simulation. The proton transport between water molecules was modeled using the second generation multistate empirical valence bond model. The proton diffusion was found to be inhibited at the membrane surface. The potential of mean force for the proton adsorption to the membrane surface and its release back into the bulk water was also determined, yielding a small barrier in each direction. An efficient algorithm for Ewald summation calculations for the multistate empirical valence bond model is also introduced.

Adsorption↗