A polarizable ellipsoidal force field for halogen bonds

Abstract

The anisotropic effects and short-range quantum effects are essential characters in the formation of halogen bonds. Since there are an array of applications of halogen bonds and much difficulty in modeling them in classical force fields, the current research reports solely the polarizable ellipsoidal force field (PEff) for halogen bonds. The anisotropic charge distribution was represented with the combination of a negative charged sphere and a positively charged ellipsoid. The polarization energy was incorporated by the induced dipole model. The resulting force field is "physically motivated," which includes separate, explicit terms to account for the electrostatic, repulsion/dispersion, and polarization interaction. Furthermore, it is largely compatible with existing, standard simulation packages. The fitted parameters are transferable and compatible with the general AMBER force field. This PEff model could correctly reproduces the potential energy surface of halogen bonds at MP2 level. Finally, the prediction of the halogen bond properties of human Cathepsin L (hcatL) has been found to be in excellent qualitative agreement with the cocrystal structures.

Leveraging Symmetries of Static Atomic Multipole Electrostatics in Molecular Dynamics Simulations

“…26 Other efforts to better reproduce σ holes in computer modeling include the work of Ibrahim on off-site point charges, 37 as well as careful electrostatic calculations from the SIBFA model 38 and a recently published polarizable ellipsoidal force field. 39 Our PC and MTP parametrizations of pyrrole did not reproduce the experimental hydration free energy as well as for the other compounds, mostly due to the use of benzene's hydrogen atom type for pyrrole's amine. Clearly, the two types of hydrogens generate very different types of chemistry, which our PC and MTP force fields do distinguish (to the extent of the methods' resolutions).…”

Application of polarizable ellipsoidal force field model to pnicogen bonds

“…The two‐body repulsive and dispersion interaction ( V rd ), and the polarization interaction ( V pol ) are the same as those in the original PEff model . The steepness parameter λ was set to 1.3, which was very close to that for halogen bond.…”

“…A more sophisticated electrostatic model, the polarizable multipoles model was proposed recently to accurately describe the electrostatics in these noncovalent bonds . We previously reported a polarizable ellipsoidal force field (PEff) model to determine the halogen bonding interaction where the anisotropic charge distribution was represented with a negatively charged sphere and a positively charged ellipsoid . The results indicate that the model can correctly reproduce the potential energy surface of halogen bonds at MP2 level.…”

Molecular dynamics simulation of halogen bonding mimics experimental data for cathepsin L inhibition

“…Other methodologies are being developed with the expectation that they will be able to provide conclusive evidence for the participation of these interactions in the affinity of specific halogenated molecules with their biological targets. Thus, several groups have developed modified force fields that have been tested in small models, though not yet with specific biological systems [17][18][19][20][21][22]. Endeavors of this sort naturally require biochemical-pharmacological data allowing experimental affinities to be compared with theoretically calculated parameters.…”