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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM093937-03
Application #
8306085
Study Section
Biodata Management and Analysis Study Section (BDMA)
Program Officer
Brazhnik, Paul
Project Start
2010-08-10
Project End
2015-07-31
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
3
Fiscal Year
2012
Total Cost
$437,203
Indirect Cost
$100,965
Name
Clemson University
Department
Physics
Type
Schools of Engineering
DUNS #
042629816
City
Clemson
State
SC
Country
United States
Zip Code
29634
Decherchi, Sergio; Masetti, Matteo; Vyalov, Ivan et al. (2015) Implicit solvent methods for free energy estimation. Eur J Med Chem 91:27-42
Li, Minghui; Petukh, Marharyta; Alexov, Emil et al. (2014) Predicting the Impact of Missense Mutations on Protein-Protein Binding Affinity. J Chem Theory Comput 10:1770-1780
Nedumpully-Govindan, Praveen; Li, Lin; Alexov, Emil G et al. (2014) Structural and energetic determinants of tyrosylprotein sulfotransferase sulfation specificity. Bioinformatics 30:2302-9
Colmenares, Jose; Ortiz, Jesus; Rocchia, Walter (2014) GPU linear and non-linear Poisson-Boltzmann solver module for DelPhi. Bioinformatics 30:569-70
Masetti, Matteo; Rocchia, Walter (2014) Molecular mechanics and dynamics: numerical tools to sample the configuration space. Front Biosci (Landmark Ed) 19:578-604
Li, Lin; Li, Chuan; Alexov, Emil (2014) On the Modeling of Polar Component of Solvation Energy using Smooth Gaussian-Based Dielectric Function. J Theor Comput Chem 13:
Boccuto, Luigi; Aoki, Kazuhiro; Flanagan-Steet, Heather et al. (2014) A mutation in a ganglioside biosynthetic enzyme, ST3GAL5, results in salt & pepper syndrome, a neurocutaneous disorder with altered glycolipid and glycoprotein glycosylation. Hum Mol Genet 23:418-33
Campbell, Brandon; Petukh, Marharyta; Alexov, Emil et al. (2014) On the electrostatic properties of homodimeric proteins. J Theor Comput Chem 13:
Dias, Roberta P; Li, Lin; Soares, Thereza A et al. (2014) Modeling the electrostatic potential of asymmetric lipopolysaccharide membranes: the MEMPOT algorithm implemented in DelPhi. J Comput Chem 35:1418-29
Colmenares, José; Galizia, Antonella; Ortiz, Jesús et al. (2014) A combined MPI-CUDA parallel solution of linear and nonlinear Poisson-Boltzmann equation. Biomed Res Int 2014:560987

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