The goal of this project is to maintain and further develop the existing software DelPhi (http://wiki.c2b2.columbia.edu/honiglab_public/index.php/Software:DelPhi). DelPhi provides numerical solutions to the Poisson-Boltzmann Equation (PBE) (both linear and non-linear forms) and calculates the corresponding energies for molecules and geometric objects immersed in water and salt phase or another continuum medium. Electrostatic forces are essential for the function, stability and interactions of virtually all biological macromolecules because most biological macromolecules, especially DNA and RNA, are highly charged. The role of electrostatics is two fold: providing long-range interactions steering biological molecules toward their pre-binding orientations and contributing to the specificity by strong short-range direct interactions. In addition, many biologically important effects such as pH and salt dependence effects are primarily electrostatic in nature. Moreover, the constant progress of nanotechnology requires modeling of systems made of biological molecules and charged metal/dielectric surfaces and objects. Thus, accurate calculations of electrostatic fields and energies are crucial for successful modeling of virtually all biological processes and many other phenomena occurring in nanosystems and nanodevices. We propose to maintain and further develop the DelPhi, the first PB solver used by many researchers as is shown in the main body of the proposal. In addition to the existing features such as assigning different dielectric constants to different regions of space, modeling geometrical objects and charge distributions, treating systems containing mixed salt solutions, we plan to develop new options as modeling implicit/explicit membrane, predicting explicit ion binding and new geometrical objects. In parallel we will modernize the code and the corresponding algorithms and will facilitate interactions with our users.
Electrostatics is essential for function, stability and interactions of virtually all biological macromolecules, including receptor-drug recognition. The central role of electrostatics is due to the fact that most biological macromolecules are highly charged, because they contain many charged amino acids which in turn are essential for structure, function and interactions of variety of biomolecules. Many biologically important effects such as pH and salt dependence effects are primarily electrostatic in nature. Therefore an accurate modeling of electrostatic potential and the corresponding energies is critical for successful drug discovery and optimization. Relevance to Human Health (Project narrative) Electrostatics is essential for function, stability and interactions of virtually all biological macromolecules, including receptor-drug recognition. The central role of electrostatics is due to the fact that most biological macromolecules are highly charged, because they contain many charged amino acids which in turn are essential for structure, function and interactions of variety of biomolecules. Many biologically important effects such as pH and salt dependence effects are primarily electrostatic in nature. Therefore an accurate modeling of electrostatic potential and the corresponding energies is critical for successful drug discovery and optimization.
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