Transferability and reproducibility in electron-density studies – bond-topological and atomic properties of tripeptides of the type L-alanyl-X-L-alanine

Abstract

In the last decade three different data bank approaches have been developed that are intended to make electron-density examinations of large biologically important molecules possible. They rely on Bader's concept of transferability of submolecular fragments with retention of their electronic properties. Therefore, elaborate studies on the quantification of transferability in experiment and theory are still very important. Tripeptides of the type L-alanyl-X-L-alanine (X being any of the 20 naturally encoded amino acids) serve as a model case between amino acids and proteins. The two experimental electron-density determinations (L-alanyl-L-histidinyl-L-alanine and L-alanyl-L-phenylalanyl-L-alanine, highly resolved synchrotron X-ray diffraction data sets) performed in this study and theoretical calculations on all 20 different L-alanyl-X-L-alanine molecules contribute to a better estimation of transferability in the peptide case. As a measure of reproducibility and transferability, standard deviations from averaging over bond-topological and atomic properties of atoms or bonds that are considered equal in their chemical environments were calculated. This way, transferability and reproducibility indices were introduced. It can be shown that experimental transferability indices generally slightly exceed experimental reproducibility indices and that these larger deviations can be attributed to chemical effects such as changes in the geometry (bond lengths and angles), the polarization pattern and the neighboring sphere due to crystal packing. These effects can partly be separated from each other and quantified with the help of gas-phase calculations at optimized and experimental geometries. Thus, the degree of transferability can be quantified in very narrow limits taking into account experimental errors and chemical effects.

The generalized invariom database (GID)

“…Transferability can be assumed when charges agree within a certain standard deviation, as shown for some examples in . The study of transferability of theoretical QTAIM atomic charges and volumes was complemented by comparison of bond topological properties from experimental electron densities (Dittrich et al, 2002;Rö del et al, 2006;Grabowsky et al, 2009). Underlying atomic multipole population parameters show a very good agreement in a similar chemical environment.…”

The Electron Density Distribution in Crystals of η6–[1,4–dihydrospiro(2H–3,1–benzoxazine–2,1′–cyclohexane)]tricarbonylchromium(0): Experiment vs Molecular Invariom

“…Therefore, the question arises how correctly to use them in the coordination sphere of metal atoms. To answer this question, we calculated the transferability index according to the published procedure for known arene tricarbonyl complexes of chromium(0) (Table S). The transferability indexes for the Cr‐C bonds are 0.007 a.u.…”

Electron Density Study Of The Anti-Alzheimer’s Disease Drug Donepezil From Conventional X-Ray Data And Invariom Database Application

“…ED values and the Laplacians at the BCPs (r[r BCP ], ∇ 2 r[r BCP ]) provide quantitative information about the strength and nature of a bond. Experimental values and the two theoretical calculations [16] Electron density study of the anti-Alzheimer's drug donepezil | Preliminary CommuniCation www.future-science.com ideal bisecting line in most cases by less then 0.1 eÅ -3 , a discrepancy that is generally tolerated with respect to the uncertainly of ED values on the BCPs [17,18].…”