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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.


Polarization energy between two particles with charges±0.5e and polarizability of 2.0 Å3 as a function of distancebetween their centers.
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fig11: Polarization energy between two particles with charges±0.5e and polarizability of 2.0 Å3 as a function of distancebetween their centers.

Mentions: Let us consider the followingillustration. Given in Figure 11 are polarizationenergies calculated for two particles—onewith a charge of +0.5 e, the other with a charge of −0.5 e,and both with polarizabilities of 2.0 Å3—asa function of distance between them. These calculations were performedfor the full-scale (eq 3), the second-order(POSSIM, eq 4b), and the first-order (eq 4a) polarizability approaches. It can be seen thatsignificant deviations occur only at short distances, especially ifwe consider only the full and second-order techniques. At a distanceof 2.6 Å, the difference between the two is already ca. 5%, andany deviation at shorter (but still physically relevant) distancescan be corrected by proper second-order parametrization. Moreover,the rapid growth in the magnitude of the full-scale polarization energyat short distances is likely to take place in the region where thepoint-dipole approximation is already less valid. Consider for example,at 1.6 Å the full polarization energy is −1076.32 kcal/mol,much too large to be physically reliable. Therefore, we believe thatour second-order model is a robust way to represent many-body interactionsthat is validated by its ability to reproduce both the gas-phase andliquid-state results.


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)

Polarization energy between two particles with charges±0.5e and polarizability of 2.0 Å3 as a function of distancebetween their centers.
© Copyright Policy
Related In: Results  -  Collection

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

fig11: Polarization energy between two particles with charges±0.5e and polarizability of 2.0 Å3 as a function of distancebetween their centers.
Mentions: Let us consider the followingillustration. Given in Figure 11 are polarizationenergies calculated for two particles—onewith a charge of +0.5 e, the other with a charge of −0.5 e,and both with polarizabilities of 2.0 Å3—asa function of distance between them. These calculations were performedfor the full-scale (eq 3), the second-order(POSSIM, eq 4b), and the first-order (eq 4a) polarizability approaches. It can be seen thatsignificant deviations occur only at short distances, especially ifwe consider only the full and second-order techniques. At a distanceof 2.6 Å, the difference between the two is already ca. 5%, andany deviation at shorter (but still physically relevant) distancescan be corrected by proper second-order parametrization. Moreover,the rapid growth in the magnitude of the full-scale polarization energyat short distances is likely to take place in the region where thepoint-dipole approximation is already less valid. Consider for example,at 1.6 Å the full polarization energy is −1076.32 kcal/mol,much too large to be physically reliable. Therefore, we believe thatour second-order model is a robust way to represent many-body interactionsthat is validated by its ability to reproduce both the gas-phase andliquid-state results.

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.