A Theoretical Databank of Transferable Aspherical Atoms and Its Application to Electrostatic Interaction Energy Calculations of Macromolecules

Abstract

Abstract:A comprehensive version of the theoretical databank of transferable aspherical pseudoatoms is described, and its first application to protein-ligand interaction energies is discussed. The databank contains all atom types present in natural amino acid residues and other biologically relevant molecules. Each atom type results from averaging over a family of chemically unique pseudoatoms, taking into account both first and second neighbors. The spawning procedure is used to ensure that close transferability is obeyed. The databank is applied to the syntenin PDZ2 domain complexed with four-residue peptides and to the PDZ2 dimer. Analysis of the electrostatic interactions energies calculated by the exact-potential/multipolemoment-databank method stresses the importance of the P 0 and P -2 residues of the peptide in establishing the interaction, whereas the P -1 residue is shown to play a much smaller role. Unexpectedly, the charged P -3 residue contributes significantly to the interaction. The class I and II peptides are bound with the same strength by the syntenin PDZ2 domain, though the electrostatic interaction energy of the P -2 residue is smaller for class I peptides. There is no difference between the interaction energies of the peptides with PDZ2 domains from singledomain protein fragments and those from PDZ1-PDZ2 tandems.

Extracting water and ion distributions from solution x-ray scattering experiments

“…(It should be noted that there are lots of work done to incorporate the anisotropicity and asphericity of electron density in order to minimize the deformation density, for example, see Refs. [81][82][83].) The density is thus computed by summing up the contribution of all the atoms.…”

The active site of hen egg-white lysozyme: flexibility and chemical bonding

“…the C atom in alanine) are nearly the same in all compounds containing this atom (Pichon-Pesme et al, 1995). Based on this principle, several databases of transferable multipole parameters have been developed (PichonPesme et al, 1995(PichonPesme et al, , 2004Volkov et al, 2004;Dittrich et al, 2006;Zarychta et al, 2007;Dominiak et al, 2007Dominiak et al, , 2009Domagała et al, 2012). They offer the possibility of constructing a multipole model of any molecule without the need to refine parameters beyond those of the IAM, i.e.…”

New version of UBDB databank andLSDBprogram, verification and applications

“…The theoretical databank of aspherical pseudoatoms (UBDB) has been designed as a set of parameters to be used in standard refinement of crystal structures, as a starting point in high-resolution studies, or also in reconstruction of molecular densities and the evaluation of a number of electrostatic properties of studied molecules. The UBDB consists of all atom types found in peptides, proteins and some other biologically relevant molecules [1]. It had been already shown that the databank corresponds very well to the electron density in a number of amino acids, when compared to conventional ab initio methods at the B3LYP/6-31G** level, and also, reproduces the electrostatic interaction energies quite well (~1kcal per mole).…”

“…The MDs were obtained through Fourier space fitting of pseudoatom model to the electron densities resulting from ab initio DFT calculations at B3LYP/6-31G** level. Such procedure was selected in order to be compatible with the idea of building a pseudoatom database [1][2][3] pursued in the charge density crystallography. Atomic multipole moments expressed in local coordinate system were calculated on the basis of three density partitions: directly from pseudoatoms, from atomic densities computed via stockholder partitioning and from atomic basins derived via topological analysis.…”

“…The atom types' definitions were modified and new atom keys added to provide more precise description of the atomic charge distribution. H-X bond lengths were updated according to Allen et al (2010) [2] and implemented in the LSDB program as well as used for modelling the appropriate atom types. The new version of LSDB and databank is available on the website [3].…”