Design of a reduced point charge model for proteins – Molecular Dynamics applications

To model and simulate large molecular systems like proteins, the development of reduced representations is currently an active field of research. In a previous work [1], we developed an approach to locate minima and maxima in a smoothed charge density field ρsm calculated through the Poisson equation:



where Φsm is the corresponding smoothed molecular electrostatic potential (MEP) built from a set of atomic charges [2]. More particularly, the approach has been applied to the design of amino acid (AA) reduced point charge models (Figure).
The AA models allow to reproduce protein MEP maps, and additionally, provide solvation free energies obtained using the program APBS [3] that are in good agreement, when all-atom molecular surfaces are used, with the all-atom ones. The new charges and interaction parameters have additionally been implemented in the program TINKER [4] to carry out molecular dynamics simulations of polypeptides [5].
Reduced point charge model of triptophan as obtained from a smoothed Amber99-based charge density distribution function.

References:

1. Leherte, L., Vercauteren, D.P. J. Comput.-Aided Mol. Des., 25 (2011) 913-930.
2. Leherte, L., Vercauteren, D.P. J. Chem. Theory Comput., 5 (2009) 3279-3298.
3. Baker, N.A., Sept, D., Joseph, S., Holst, M.J., McCammon, J.A. Proc. Natl. Acad. Sci. USA, 98 (2001) 10037-10041.
4. TINKER - Software Tools for Molecular Design, http://dasher.wustl.edu/tinker/
5. Leherte, L., Vercauteren, D.P. J. Phys. Chem. A, 115 (2011) 12531-12543.