Coarse Point Charge Models For Proteins From Smoothed Molecular Electrostatic Potentials

Abstract

To generate coarse electrostatic models of proteins, we developed an original approach to hierarchically locate maxima and minima in smoothed molecular electrostatic potentials. A charge-fitting program was used to assign charges to the so-obtained reduced representations. Templates are defined to easily generate coarse point charge models for protein structures, in the particular cases of the Amber99 and Gromos43A1 force fields. Applications to four small peptides and to the ion channel KcsA are presented. Electrostatic potential values generated by the reduced models are compared with the corresponding values obtained using the original sets of atomic charges.

Charge density distributions derived from smoothed electrostatic potential functions: design of protein reduced point charge models

“…The implementation of the iterative search of the extrema in the molecular CD distribution function, i.e., the CD function derived from the MEP calculated using all atomic charges, led to results that were very similar to those obtained previously [51], i.e., smoothed MEPs with extrema that were located, as illustrated further in the text, away from the molecular skeleton. In order to generate points located on or close to the molecular structure, extrema are now searched for in two separate stages, i.e., from the CD distribution built through Eq.…”

“…Calculation of CG point charges CG charge values were obtained using the charge fitting program QFIT [60] as already detailed previously [51]. All-atom MEP grids were built using the Coulomb law, for a system in vacuum, considering Amber99 point charges [54] assigned using the software PDB2PQR [61,62], with a grid step of 0.5 Å .…”

“…Following the development of our approach to hierarchically decompose a protein structure into fragments from its ED distribution [49,50], the method was applied to MEPs, calculated from point charges as implemented in well-known FFs [51]. The procedure allowed to locate minima and maxima in a smoothed MEP to design AA reduced point charge models.…”

“…In this paper, we will show that using the extrema of CD distribution functions rather than those of MEPs [51] allows to overcome the drawbacks mentioned above, particularly when extrema are located in distributions q A,t that are calculated from MEPs built on negative and positive charges separately, as later detailed. The new AA models allow to reproduce protein MEP maps, and additionally, provide solvation free energies as obtained using the program APBS [52,53] that are in close agreement with the all-atom ones.…”

“…The new AA models allow to reproduce protein MEP maps, and additionally, provide solvation free energies as obtained using the program APBS [52,53] that are in close agreement with the all-atom ones. The charge values allowing the calculation of the initial all-atom MEP U function are taken from the Amber99 FF [54] to allow comparisons with previous results [51]. Applications were achieved on rigid structures retrieved from the Protein Data Bank (PDB) [55,56], i.e., four small peptides (PDB access codes 1BC5, 1BXX, 2EVQ, 2RD4), a set of 53 protein structures as listed in [57], and four KcsA channel structures (PDB access codes 1BL8, 1S5H, 2ATK, 2P7T).…”