Analytical Polarizable Continuum Model for Wavelets on NURBS Patches

This article concerns the application of wavelet techniques on molecular surfaces constituted of four-sided patches. The Polarizable Continuum Model, which is governed by the Poisson-Boltzmann equation, is treated by means of boundary integral equations. The media inside and outside the molecular surface consist respectively of the solute and the solvent. For a given electrically charged molecule, the principal unknown is the electrostatic solvation energy when the permittivity is specified. The wavelet basis functions are constructed on the unit square which are subsequently mapped onto the patches that are assumed to be isotropically shaped and to admit similar surface areas. The initial transmission problem is recast as an integral equation in term of both the single and the double layers. Domain decomposition preconditioner serves as acceleration of the linear solver of the single layer which is badly conditioned.

非线性及粒子空间效应对交流电渗流泵的影响

在交流电渗流(ACEO)泵的研究中,一般采用Debye-Huckel(D-H)线性近似法。但该方法只在电压很小时才成立,这和实际情况不符;此外,交流电渗流泵在大电压、高频率下的反向流现象也不能由D-H近似法给出正确的预测。当电压较大时,一般采用非线性的Poisson-Boltzmann(P-B)模型。但是,P-B模型也无法对交流电渗流泵在大电压、高频率下的反向流现象进行预测。在P-B模型中,溶液粒子被当作一个空间点,忽略了粒子间的相互作用以及粒子本身的空间体积效应。实际的粒子都有一定的空间体积,当电压较大、溶液浓度较高时,粒子的空间体积不应被忽略。由于粒子的空间体积,通过引入粒子空间效应对P-B模型进行修正后,给出了交流电渗流泵在较大电压下的数值模型,并对交流电渗流泵在较大电压下的高频率反向流现象进行了成功的预测。

Rupintrivir is a promising candidate for treating severe cases of Enterovirus-71 infection

AIM:To evaluate the suitability of rupintrivir against Enterovirus 71(EV71)induced severe clinical symptoms using computational methods. METHODS:The structure of EV71 3C protease was predicted by homology modeling.The binding free energies between rupintrivir and EV71 3C and human rhinovirus 3C protease were computed by molecular dynamics and molecular mechanics Poisson-Boltzmann/ surface area and molecular mechanics generalized-born/ surface area methods.EV71 3C fragments obtained from clinical samples collected during May to July 2008 in Shanghai were amplified by reverse-transcription and polymerase chain reaction and sequenced. RESULTS:We observed that rupintrivir had favorable binding affinity with EV71 3C protease(-10.76 kcal/mol). The variability of the 3C protein sequence in isolates of various outbreaks,including those obtained in our hospital from May to July 2008,were also analyzed to validate the conservation of the drug binding pocket. CONCLUSION:Rupintrivir,whose safety profiles had been proved,is an attractive candidate and can be quickly utilized for treating severe EV71 infection.

On Applicability of Poisson-Boltzmann Equation for Micro-and Nanoscale Electroosmotic Flows

The applicability of the Poisson-Boltzmann model for micro-and nanoscale electroosmotic flows is a very important theoretical and engineering problem.In this contribution we investigate this problem at two aspects:first the high ionic concentration effect on the Boltzmann distribution assumption in the diffusion layer is studied by comparisons with the molecular dynamics(MD)simulation results;then the electrical double layer(EDL)interaction effect caused by low ionic concentrations in small channels is discussed by comparing with the dynamic model described by the coupled Poisson-Nernst-Planck(PNP)and Navier-Stokes(NS)equations.The results show that the Poisson-Boltzmann(PB)model is applicable in a very wide range:(i)the PB model can still provide good predictions of the ions density profiles up to a very high ionic concentration(∼1 M)in the diffusion layer;(ii)the PB model predicts the net charge density accurately as long as the EDL thickness is smaller than the channel width and then overrates the net charge density profile as the EDL thickness increasing,and the predicted electric potential profile is still very accurate up to a very strong EDL interaction(λ/W∼10).

Image Charge Methods for a Three-Dielectric-Layer Hybrid Solvation Model of Biomolecules

This paper introduces a three dielectric layer hybrid solvation model for treating electrostatic interactions of biomolecules in solvents using the PoissonBoltzmann equation.In this model,an interior spherical cavity will contain the solute and some explicit solvent molecules,and an intermediate buffer layer and an exterior layer contain the bulk solvent.A special dielectric permittivity profile is used to achieve a continuous dielectric transition from the interior cavity to the exterior layer.The selection of this special profile using a harmonic interpolation allows an analytical solution of the model by generalizing the classical Kirkwood series expansion.Discrete image charges are used to speed up calculations for the electrostatic potential within the interior and buffer layer regions.Semi-analytical and least squares methods are used to construct an accurate discrete image approximation for the reaction field due to solvent with or without salt effects.In particular,the image charges obtained by the least squares method provide accurate approximations to the reaction field independent of the ionic concentration of the solvent.Numerical results are presented to validate the accuracy and effectiveness of the image charge methods.

The Geometry Behind Numerical Solvers of the Poisson-Boltzmann Equation

Electrostatics interactions play a major role in the stabilization of biomolecules:as such,they remain a major focus of theoretical and computational studies in biophysics.Electrostatics in solution is strongly dependent on the nature of the solvent and on the ions it contains.While methods that treat the solvent and ions explicitly provide an accurate estimate of these interactions,they are usually computationally too demanding to study large macromolecular systems.Implicit solvent methods provide a viable alternative,especially those based on Poisson theory.The Poisson-Boltzmann equation(PBE)treats the system in a mean field approximation,providing reasonable estimates of electrostatics interactions in a solvent treated as continuum.In the first part of this paper,we review the theory behind the PBE,including recent improvement in which ions size and dipolar features of solvent molecules are taken into account explicitly.The PBE is a non linear second order differential equation with discontinuous coefficients,for which no analytical solution is available for large molecular systems.Many numerical solvers have been developed that solve a discretized version of the PBE on a mesh,either using finite difference,finite element,or boundary element methods.The accuracy of the solutions provided by these solvers highly depend on the geometry of their underlying meshes,as well as on the method used to embed the physical system on the mesh.In the second part of the paper,we describe a new geometric approach for generating unstructured tetrahedral meshes as well as simplifications of these meshes that are well fitted for solving the PBE equation using multigrid approaches.

Ionic effects on the transport characteristics of nanowire-based FETs in a liquid environment

For the development of ultra-sensitive electrical bio/chemical sensors based on nanowire field effect transistors （FETs）, the influence of the ions in the solution on the electron transport has to be understood. For this purpose we establish a simulation platform for nanowire FETs in the liquid environment by implementing the modified Poisson-Boltzmann model into Landauer transport theory. We investigate the changes of the electric potential and the transport characteristics due to the ions. The reduction of sensitivity of the sensors due to the screening effect from the electrolyte could be successfully reproduced. We also fabricated silicon nanowire Schottky-barrier FETs and our model could capture the observed reduction of the current with increasing ionic concentration. This shows that our simulation platform can be used to interpret ongoing experiments, to design nanowire FETs, and it also gives insight into controversial issues such as whether ions in the buffer solution affect the transport characteristics or not.

DelPhi Web Server:A Comprehensive Online Suite for Electrostatic Calculations of Biological Macromolecules and Their Complexes

Here we report a web server,the DelPhi web server,which utilizes DelPhi program to calculate electrostatic energies and the corresponding electrostatic potential and ionic distributions,and dielectric map.The server provides extra services to fix structural defects,as missing atoms in the structural file and allows for generation of missing hydrogen atoms.The hydrogen placement and the corresponding DelPhi calculations can be done with user selected force field parameters being either Charmm22,Amber98 or OPLS.Upon completion of the calculations,the user is given option to download fixed and protonated structural file,together with the parameter and Delphi output files for further analysis.Utilizing Jmol viewer,the user can see the corresponding structural file,to manipulate it and to change the presentation.In addition,if the potential map is requested to be calculated,the potential can be mapped onto the molecule surface.The DelPhi web server is available from http://compbio.clemson.edu/delphi webserver.