Sankolli, Ravish, Malaspina, Lorraine, Dolomanov, Oleg, Luger, Peter, Holstein, Julian, Morgenroth, Wolfgang, Paulmann, Carsten, Kleemis, Florian and Grabowsky, Simon (2025) Role of restraints on hydrogen atoms in Hirshfeld Atom Refinement: the case of tri-aspartic acid trihydrate. Acta crystallographica. Section.B structural science., 81 (5). pp. 484-497. ISSN 1600-5740; 0108-7681

Abstract

Two polymorphs of L-Asp-L-Asp-L-Asp (DDD) trihydrate were investigated with the quantum-crystallographic refinement technique Hirshfeld Atom Refinement (HAR) as model compounds for biologically important proton-shuttle reactions. With HAR, hydrogen atom positions were refined freely against the X-ray diffraction data and yielded X-H bond distances close to those from neutron diffraction. However, the X-ray data of DDD trihydrate do not carry enough information to refine hydrogen atom anisotropic displacement parameters (ADPs), while they are considered to be of similar quality as normal oligopeptide or protein datasets, including disordered fragments. Therefore, ISOR, SIMU, DELU, and RIGU restraints were tested for the hydrogen atom ADPs. Although it was found that there is no significant influence of the restraint weights and corresponding ADP values on the X-H distances, some recommendations on hydrogen atom ADP restraint weights to be used in HAR are given. For ISOR, the suggested values are 10 times smaller (stricter) than the default values for non-hydrogen atoms in IAM refinements, whereas those for RIGU are suggested to be less strict.

Item Type:	Article
Keywords:	Hydrogen atoms; Restraints; Hirshfeld Atom Refinement; Crystal water
Date Deposited:	12 Nov 2025 00:45
Last Modified:	12 Nov 2025 00:45
URI:	https://oak.novartis.com/id/eprint/55409