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Optimized Halogen Atomic Radii for PBSA Calculations Using Off-Center Point-Charges

preprint
submitted on 14.02.2021, 19:13 and posted on 16.02.2021, 12:59 by Andreia Fortuna, Paulo J. Costa
In force field methods, the usage of off-center point-charges, also called extra-points (EPs), is a common strategy to tackle the anisotropy of the electrostatic potential of covalently-bonded halogens (X), thus allowing the description of halogen bonds (XBs) at the molecular mechanics / molecular dynamics (MM/MD) level. Diverse EP implementations exist in the literature differing on the charge sets and/or the X–EP distances. Poisson–Boltzmann and surface area (PBSA) calculations can be used to obtain solvation free energies (∆G solv ) of small molecules, often to compute binding free energies (∆G bind ) at the MM PBSA level. This method depends, among other parameters, on the empirical assignment of atomic radii (PB radii). Given the multiplicity of off-center point-charges models and the lack of specific PB radii for halogens compatible with such implementations, in this work we assessed the performance of PBSA calculations for the estimation of ∆G solv values in water (∆G hyd ), also conducting an optimization of the halogen PB radii (Cl, Br, and I) for each EP model. We not only expand the usage of EP models in the scope of the General AMBER Force Field (GAFF) but also provide the first optimized halogen PB radii in the context of the CHARMM General Force Field (CGenFF), thus contributing to improving the description of halogenated compounds in PBSA calculations.

Funding

SFRH/BD/146447/2019

UIDB/04046/2020

UIDP/04046/2020

UID/DTP/04138/2019

LISBOA-01-0145-FEDER- 028455

PTDC/QUI-QFI/28455/2017

History

Email Address of Submitting Author

pjcosta@ciencias.ulisboa.pt

Institution

BioISI – Biosystems & Integrative Sciences Institute, Faculty of Sciences, University of Lisboa

Country

Portugal

ORCID For Submitting Author

0000-0002-0492-6666

Declaration of Conflict of Interest

The authors declare no conflict of interest

Version Notes

Draft ver1

Exports