title: Realistic sampling of amino acid geometries for a multipolar polarizable force field.
abstract: The Quantum Chemical Topological Force Field (QCTFF) uses the machine learning method kriging to map atomic multipole moments to the coordinates of all atoms in the molecular system. It is important that kriging operates on relevant and realistic training sets of molecular geometries. Therefore, we sampled single amino acid geometries directly from protein crystal structures stored in the Protein Databank (PDB). This sampling enhances the conformational realism (in terms of dihedral angles) of the training geometries. However, these geometries can be fraught with inaccurate bond lengths and valence angles due to artefacts of the refinement process of the X-ray diffraction patterns, combined with experimentally invisible hydrogen atoms. This is why we developed a hybrid PDB/nonstationary normal modes (NM) sampling approach called PDB/NM. This method is superior over standard NM sampling, which captures only geometries optimized from the stationary points of single amino acids in the gas phase. Indeed, PDB/NM combines the sampling of relevant dihedral angles with chemically correct local geometries. Geometries sampled using PDB/NM were used to build kriging models for alanine and lysine, and their prediction accuracy was compared to models built from geometries sampled from three other sampling approaches. Bond length variation, as opposed to variation in dihedral angles, puts pressure on prediction accuracy, potentially lowering it. Hence, the larger coverage of dihedral angles of the PDB/NM method does not deteriorate the predictive accuracy of kriging models, compared to the NM sampling around local energetic minima used so far in the development of QCTFF.
authors.affiliation: Manchester Institute of Biotechnology (MIB), 131 Princess Street, Manchester, M1 7DN, Great Britain.|School of Chemistry, University of Manchester, Oxford Road, Manchester, M13 9PL, Great Britain.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Hughes
authors.affiliation: Manchester Institute of Biotechnology (MIB), 131 Princess Street, Manchester, M1 7DN, Great Britain.|School of Chemistry, University of Manchester, Oxford Road, Manchester, M13 9PL, Great Britain.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cardamone
authors.affiliation: Manchester Institute of Biotechnology (MIB), 131 Princess Street, Manchester, M1 7DN, Great Britain.|School of Chemistry, University of Manchester, Oxford Road, Manchester, M13 9PL, Great Britain.
authors.forename: Paul L A
authors.initials: PL
authors.lastname: Popelier
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D011487:Protein Conformation
chemical_list: D000596:Amino Acids
keywords: conformational sampling; electrostatics; kriging; protein data bank; quantum chemical topology; quantum theory of atoms in molecules