Biomedical subjects

Grigori Sigalov

Publications and source records attributed to Grigori Sigalov.

3 recordsLinked to original sources

PubMed2006

Analytical electrostatics for biomolecules: beyond the generalized Born approximation.

The modeling and simulation of macromolecules in solution often benefits from fast analytical approximations for the electrostatic interactions. In our previous work [G. Sigalov et al., J. Chem. Phys. 122, 094511 (2005)], we proposed a method based on an approximate analytical solution of the linearized Poisson-Boltzmann equation for a sphere. In the current work, we extend the method to biomolecules of arbitrary shape and provide computationally efficient algorithms for estimation of the parameters of the model. This approach, which we tentatively call ALPB here, is tested against the standard numerical Poisson-Boltzmann (NPB) treatment on a set of 579 representative proteins, nucleic acids, and small peptides. The tests are performed across a wide range of solvent/solute dielectrics and at biologically relevant salt concentrations. Over the range of the solvent and solute parameters tested, the systematic deviation (from the NPB reference) of solvation energies computed by ALPB is 0.5-3.5 kcal/mol, which is 5-50 times smaller than that of the conventional generalized Born approximation widely used in this context. At the same time, ALPB is equally computationally efficient. The new model is incorporated into the AMBER molecular modeling package and tested on small proteins.

Algorithms↗

PubMed2005

Incorporating variable dielectric environments into the generalized Born model.

A generalized Born (GB) model is proposed that approximates the electrostatic part of macromolecular solvation free energy over the entire range of the solvent and solute dielectric constants. The model contains no fitting parameters, and is derived by matching a general form of the GB Green function with the exact Green's function of the Poisson equation for a random charge distribution inside a perfect sphere. The sphere is assumed to be filled uniformly with dielectric medium epsilon(in), and is surrounded by infinite solvent of constant dielectric epsilon(out). This model is as computationally efficient as the conventional GB model based on the widely used functional form due to Still et al. [J. Am. Chem. Soc. 112, 6127 (1990)], but captures the essential physics of the dielectric response for all values of epsilon(in) and epsilon(out). This model is tested against the exact solution on a perfect sphere, and against the numerical Poisson-Boltzmann (PB) treatment on a set of macromolecules representing various structural classes. It shows reasonable agreement with both the exact and the numerical solutions of the PB equation (where available) considered as reference, and is more accurate than the conventional GB model over the entire range of dielectric values.

Journal Article↗

PubMed2003

Electrostatic nanolithography in polymers using atomic force microscopy.

The past decade has witnessed an explosion of techniques used to pattern polymers on the nano (1-100 nm) and submicrometre (100-1,000 nm) scale, driven by the extensive versatility of polymers for diverse applications, such as molecular electronics, data storage, optoelectronics, displays, sacrificial templates and all forms of sensors. Conceptually, most of the patterning techniques, including microcontact printing (soft lithography), photolithography, electron-beam lithography, block-copolymer templating and dip-pen lithography, are based on the spatially selective removal or formation/deposition of polymer. Here, we demonstrate an alternative and novel lithography technique--electrostatic nanolithography using atomic force microscopy--that generates features by mass transport of polymer within an initially uniform, planar film without chemical crosslinking, substantial polymer degradation or ablation. The combination of localized softening of attolitres (10(2)-10(5) nm3) of polymer by Joule heating, extremely non-uniform electric field gradients to polarize and manipulate the soften polymer, and single-step process methodology using conventional atomic force microscopy (AFM) equipment, establishes a new paradigm for polymer nanolithography, allowing rapid (of the order of milliseconds) creation of raised (or depressed) features without external heating of a polymer film or AFM tip-film contact.

Microscopy, Atomic Force↗