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POSSIM: Parameterizing Complete Second-Order Polarizable Force Field for Proteins.

Li X, Ponomarev SY, Sigalovsky DL, Cvitkovic JP, Kaminski GA - J Chem Theory Comput (2014)

Bottom Line: Furthermore, our fitting of the force field parameters for peptides and proteins has been streamlined compared with the previous generation of the complete polarizable force field and relied more on transferability of parameters for nonbonded interactions (including the electrostatic component).The resulting deviations from the quantum mechanical data are similar to those achieved with the previous generation; thus, the technique is robust, and the parameters are transferable.Therefore, we believe that this force field can be successfully applied in a wide variety of applications to proteins and protein-ligand complexes.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry and Biochemistry, Worcester Polytechnic Institute , Worcester, Massachusetts 01609, United States.

ABSTRACT
Previously, we reported development of a fast polarizable force field and software named POSSIM (POlarizable Simulations with Second order Interaction Model). The second-order approximation permits the speed up of the polarizable component of the calculations by ca. an order of magnitude. We have now expanded the POSSIM framework to include a complete polarizable force field for proteins. Most of the parameter fitting was done to high-level quantum mechanical data. Conformational geometries and energies for dipeptides have been reproduced within average errors of ca. 0.5 kcal/mol for energies of the conformers (for the electrostatically neutral residues) and 9.7° for key dihedral angles. We have also validated this force field by running Monte Carlo simulations of collagen-like proteins in water. The resulting geometries were within 0.94 Å root-mean-square deviation (RMSD) from the experimental data. We have performed additional validation by studying conformational properties of three oligopeptides relevant in the context of N-glycoprotein secondary structure. These systems have been previously studied with combined experimental and computational methods, and both POSSIM and benchmark OPLS-AA simulations that we carried out produced geometries within ca. 0.9 Å RMSD of the literature structures. Thus, the performance of POSSIM in reproducing the structures is comparable with that of the widely used OPLS-AA force field. Furthermore, our fitting of the force field parameters for peptides and proteins has been streamlined compared with the previous generation of the complete polarizable force field and relied more on transferability of parameters for nonbonded interactions (including the electrostatic component). The resulting deviations from the quantum mechanical data are similar to those achieved with the previous generation; thus, the technique is robust, and the parameters are transferable. At the same time, the number of parameters used in this work was noticeably smaller than that of the previous generation of our complete polarizable force field for proteins; thus, the transferability of this set can be expected to be greater, and the danger of force field fitting artifacts is lower. Therefore, we believe that this force field can be successfully applied in a wide variety of applications to proteins and protein-ligand complexes.

No MeSH data available.


Structures used to fittorsional parameters for the ionized C-terminus(a) and N-terminus (b). Similar systems were used for electrostaticallyneutral forms of the termini.
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fig6: Structures used to fittorsional parameters for the ionized C-terminus(a) and N-terminus (b). Similar systems were used for electrostaticallyneutral forms of the termini.

Mentions: In order to be able to use POSSIM insimulations of complete peptides and proteins in gas-phase and solution,we previously fitted torsional energy parameters for electrostaticallyneutral and charged proteins, with the end-groups being −COO–, −COOH, −NH3+,and −NH2.12 These parametrizationswere carried out using the structures shown in Figure 6 for the charged termini and analogous ones for the electrostaticallyneutral termini. These fragments correspond to the termini with anadjacent alanine residue. The angles for which the fitting of thetorsional parameters was carried out are marked in Figure 6. In each case, we compared POSSIM rotamer energieswith those obtained with the LMP2 quantum mechanical calculations; theangles were varied in 20° steps.


POSSIM: Parameterizing Complete Second-Order Polarizable Force Field for Proteins.

Li X, Ponomarev SY, Sigalovsky DL, Cvitkovic JP, Kaminski GA - J Chem Theory Comput (2014)

Structures used to fittorsional parameters for the ionized C-terminus(a) and N-terminus (b). Similar systems were used for electrostaticallyneutral forms of the termini.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4230370&req=5

fig6: Structures used to fittorsional parameters for the ionized C-terminus(a) and N-terminus (b). Similar systems were used for electrostaticallyneutral forms of the termini.
Mentions: In order to be able to use POSSIM insimulations of complete peptides and proteins in gas-phase and solution,we previously fitted torsional energy parameters for electrostaticallyneutral and charged proteins, with the end-groups being −COO–, −COOH, −NH3+,and −NH2.12 These parametrizationswere carried out using the structures shown in Figure 6 for the charged termini and analogous ones for the electrostaticallyneutral termini. These fragments correspond to the termini with anadjacent alanine residue. The angles for which the fitting of thetorsional parameters was carried out are marked in Figure 6. In each case, we compared POSSIM rotamer energieswith those obtained with the LMP2 quantum mechanical calculations; theangles were varied in 20° steps.

Bottom Line: Furthermore, our fitting of the force field parameters for peptides and proteins has been streamlined compared with the previous generation of the complete polarizable force field and relied more on transferability of parameters for nonbonded interactions (including the electrostatic component).The resulting deviations from the quantum mechanical data are similar to those achieved with the previous generation; thus, the technique is robust, and the parameters are transferable.Therefore, we believe that this force field can be successfully applied in a wide variety of applications to proteins and protein-ligand complexes.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry and Biochemistry, Worcester Polytechnic Institute , Worcester, Massachusetts 01609, United States.

ABSTRACT
Previously, we reported development of a fast polarizable force field and software named POSSIM (POlarizable Simulations with Second order Interaction Model). The second-order approximation permits the speed up of the polarizable component of the calculations by ca. an order of magnitude. We have now expanded the POSSIM framework to include a complete polarizable force field for proteins. Most of the parameter fitting was done to high-level quantum mechanical data. Conformational geometries and energies for dipeptides have been reproduced within average errors of ca. 0.5 kcal/mol for energies of the conformers (for the electrostatically neutral residues) and 9.7° for key dihedral angles. We have also validated this force field by running Monte Carlo simulations of collagen-like proteins in water. The resulting geometries were within 0.94 Å root-mean-square deviation (RMSD) from the experimental data. We have performed additional validation by studying conformational properties of three oligopeptides relevant in the context of N-glycoprotein secondary structure. These systems have been previously studied with combined experimental and computational methods, and both POSSIM and benchmark OPLS-AA simulations that we carried out produced geometries within ca. 0.9 Å RMSD of the literature structures. Thus, the performance of POSSIM in reproducing the structures is comparable with that of the widely used OPLS-AA force field. Furthermore, our fitting of the force field parameters for peptides and proteins has been streamlined compared with the previous generation of the complete polarizable force field and relied more on transferability of parameters for nonbonded interactions (including the electrostatic component). The resulting deviations from the quantum mechanical data are similar to those achieved with the previous generation; thus, the technique is robust, and the parameters are transferable. At the same time, the number of parameters used in this work was noticeably smaller than that of the previous generation of our complete polarizable force field for proteins; thus, the transferability of this set can be expected to be greater, and the danger of force field fitting artifacts is lower. Therefore, we believe that this force field can be successfully applied in a wide variety of applications to proteins and protein-ligand complexes.

No MeSH data available.