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Bashford Lab

MEAD: Macroscopic Electrostatics with Atomic Detail
A software suite for electrostatic calculations on biological macromolecules.

Summary

MEAD is a set of software objects for the purpose of modeling the electrostatics of molecules using a semi-macroscopic picture in which the solvent and the molecular interior have different dielectric constants, the boundary between the different dielectric regions is dependent on the detailed atomic structure of the molecule, and the electrostatic potential is determined by the Poisson-Boltzmann equation.  This version of MEAD includes modeling of a membrane as a low dielectric slab, possibly with a water-filled channel through a protein in the membrane.

MEAD is written in C++, which is a significant departure from most molecular software, which is more commonly written in Fortran or (recently) C.  My purpose in choosing C++ was to explore the object-oriented programming style that C++ facilitates and to make a software system that other people could borrow pieces from and make extensions to in a convenient way.

The MEAD suite includes programs to calculate the pKa values of sidechains and proteins, and solvation energies of small molecules. MEAD is used in the SCRF (self-consistent reaction field) protocol that is implemented in the ADF (Amsterdam Density Functional) software package available from Scientific Computing and Modeling (SCM ). SCRF is an iterative method that couples a quantum system with its polarizable continuum solvent or protein/solvent environment. SCRF with a solvent environment is discussed in Chen04, and SCRF with a protein/solvent environment is discussed in Asthagiri02. For information on obtaining SCRF in ADF, contact SCM.

MEAD is free software.  You can redistribute it and/or modify it under the terms of the GNU General Public License as published by the Free Software Foundation; either version 1, or (at your option) any later version.  For more details, see the README, INSTALLATION and COPYING files inside the distribution.  If you use MEAD in a scientific publication, please cite the papers, Bashford92 and ISCOPE97.


Download MEAD

The most recent version of MEAD is v2.2.9. New features in this version include library implementations of the solvate and solinprot applications that can be called from FORTRAN programs and capability for FDGridLevel::potint() to return a zero when a grid point is out of range rather than throwing an error. Details on these new features can be found in the NEWS file in the distribution.


The use of the MEAD programs is documented in a README file which is part of the download; and a brief description of the MEAD suite's overall design is given in ISCOPE97.  Some of the deeper physical and numerical issues are reviewed in Bashford04 and Baker06.

A related program is Paul Beroza's mcti (or xmcti), which uses a Monte Carlo method to calculated average protonations of sites given the intrinsic pKa of each site, and the matrix of site-site interactions. You can find it here.

Acknowledgments

The development of MEAD has been supported by the American Lebanese Syrian Associated Charities (ALSAC) and by the National Institutes of Health (GM045607 and GM086243).

References

Bashford92
Electrostatic Calculations of the pKa Values of Ionizable Groups in Bacteriorhodopsin
D. Bashford & K. Gerwert (1992) J Mol Biol vol. 224 pp. 473-486.
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Chen94
Incorporating Solvation Effects Into Density Functional Electronic Structure Calculations
Jun L. Chen, Louis Noodleman, David A. Case, and Donald Bashford J. Phys. Chem., 1994, 98 (43), pp 11059–11068.
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ISCOPE97
An Object-Oriented Programming Suite for  Electrostatic Effects in Biological Molecules
Donald Bashford. Yutaka Ishikawa,  Rodney R. Oldehoeft, John V. W. Reynders, and Marydell Tholburn,  editors, Scientific Computing in Object-Oriented Parallel  Environments, volume 1343 of Lecture Notes in Computer Science, pages  233-240, Berlin, 1997.
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Asthagiri02
Density Functional Study of the Mechanism of a Tyrosine Phosphatase: {I.} Intermediate Formation
Dilipkumar Asthagiri, Valerie Dillet, Tiqing Liu, Louis Noodleman, Robert L. Van Etten, and Donald Bashford, J. Am. Chem. Soc., 2002, 124 (34), pp 10225–10235.
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Baker06
Implicit Solvent Electrostatics in Biomolecular Simulation in New Algorithims for Macromolecular Simulation
Nathan A. Baker and Donald Bashford and David A. Case. Leikmuhler, Benedict and Chipot, Christophe and Elber, Ron and Laaksonen, Aatto and Mark, Allan and Schlick, Tamar and Schutte, Christophe and Skeel, Robert, eds. 2006:49:263-295  Series: Lecture Notes in Computional Science and Engineering, Springer-Verlag, publishers.
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Bashford04
Macroscopic Electrostatic Models for Protonation States in Proteins
Bashford, Donald. Frontiers in Bioscience 2004; 99:1082-1099.
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