Abstract
To generate reduced point charge models of proteins, we developed an original approach to hierarchically locate extrema in charge density distribution functions built from the Poisson equation applied to smoothed molecular electrostatic potential (MEP) functions. A charge fitting program was used to assign charge values to the so-obtained reduced representations. In continuation to a previous work, the Amber99 force field was selected. To easily generate reduced point charge models for protein structures, a library of amino acid templates was designed. Applications to four small peptides, a set of 53 protein structures, and four KcsA ion channel models, are presented. Electrostatic potential and solvation free energy values generated by the reduced models are compared with the corresponding values obtained using the original set of atomic charges. Results are in closer agreement with the original all-atom electrostatic properties than those obtained with a previous reduced model that was directly built from the smoothed MEP functions [Leherte and Vercauteren in J Chem Theory Comput 5:3279–3298, 2009].
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Abbreviations
- AA:
-
Amino acid
- AMBER:
-
Assisted model building and energy refinement
- APBS:
-
Adaptive Poisson-Boltzmann Solver
- CD:
-
Charge density
- CG:
-
Coarse grain(ed)
- COM:
-
Center of mass
- DNA:
-
Desoxyribonucleic acid
- ECEPP:
-
Empirical conformational energy program for peptides
- ED:
-
Electron density
- FF:
-
Force field
- GA:
-
Genetic algorithm
- LJ:
-
Lennard-Jones
- MC:
-
Monte Carlo
- MD:
-
Molecular dynamics
- MM:
-
Molecular mechanics
- MEP:
-
Molecular electrostatic potential
- PB:
-
Poisson-Boltzmann
- PDB:
-
Protein data bank
- rmsd:
-
Root mean square deviation
- SA:
-
Simulated annealing
- SLIRP:
-
Structural library of intrinsic residue propensities
- SMMP:
-
Simple molecular mechanics for proteins
- 3D:
-
Three-dimensional
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Acknowledgments
The authors thank the referees for very useful comments. They also acknowledge Profs. E. Clementi and M. Sansom for very fruitful discussions, as well as Prof. N. Baker for APBS assistance. The ‘‘Fonds National de la Recherche Scientifique’’ (FNRS-FRFC), the ‘‘Loterie Nationale’’ (convention no. 2.4578.02), and the ‘‘Facultés Universitaires Notre-Dame de la Paix’’ (FUNDP), are gratefully acknowledged for the use of the Interuniversity Scientific Computing Facility (ISCF) Center.
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Leherte, L., Vercauteren, D.P. Charge density distributions derived from smoothed electrostatic potential functions: design of protein reduced point charge models. J Comput Aided Mol Des 25, 913–930 (2011). https://doi.org/10.1007/s10822-011-9471-8
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DOI: https://doi.org/10.1007/s10822-011-9471-8