DFT energy optimization of a large carbohydrate: cyclomaltohexaicosaose (CA-26)

Authors: SCHNUPF, UDO - Cornell University; Momany, Frank

Submitted to: Journal of Physical Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/8/2011
Publication Date: 6/14/2012
Citation: Schnupf, U., Momany, F.A. 2012. DFT energy optimization of a large carbohydrate: cyclomaltohexaicosaose (CA-26). Journal of Physical Chemistry. 116(23):6618-6627.

Interpretive Summary: Cyclomaltohexaicosaose (CA-26) is the largest cyclodextrin (a cyclic sugar) where the geometric structure is experimentally known. Computer programs have been successfully used to model sugars, but because of its large size, CA-26 has not been modeled; until now. The research presented demonstrates the first computer based technique to define the structure of a large sugar. The structure of CA-26 is complex; it looks like a figure “8” with two helices. Through the use of the new computer program, the time needed to model the structure was greatly reduced. The model developed was compared with the structure determined through experimental methods and it was found that the model agreed with experimental results. This study is the first to present a clear path by which large carbohydrate molecules may be studied thus showing other scientists how to extend their computational studies to larger molecular systems of interest at considerably reduced cost and time.

Technical Abstract: CA-26 is the largest cyclodextrin (546 atoms) for which refined X-ray structural data is available. Because of its size, 26 D-glucose residues, it is beyond the scope of study of most ab initio or density functional methods, and to date has only been computationally examined using empirical force fields. The crystal structure of CA-26 is folded like a figure “8” into two 10 D-glucoses long anti-parallel left-handed V (Verkleisterung)-type helices with a ‘band-flip’ and “kink” at the top and bottom of the helices. DFTr methods were applied to CA-26 to determine if a carbohydrate molecule of this size could be calculated, and would it show structural variances from dispersion and/or solvation. The DFTr reduced basis set method developed by the authors uses 4-31G on the carbon atoms of the glucose rings and 6-31+G* on all the other atoms. B3LYP is the density functional used as a test, and after successfully optimizing CA-26 other density functionals were applied including the self-consistent charge density functional tight binding (SCC-DFTB), the B97D (dispersion corrected), and B97D-PCM (dispersion + implicit solvent) methods. Heavy atom coordinates were taken from one x-ray structure, fitted with hydrogen atoms, and geometry optimized using PM3 followed by B3LYP/6-31+G*/4-31G optimization. After optimization, the heavy atom RMS deviation of the optimized DFTr (B3LYP) structure to the crystal structure was 0.89Å, RMSD of B97D optimization was 1.38Å, B97D-PCM was 0.95Å, and SCC-DFTB was 0.94Å. These results are very good considering that no explicit water molecules were included in the computational analysis and there were ~32-38 water molecules around each CA-26 molecule in the crystal structure. Tables of internal coordinates and puckering parameters are compared to the x-ray structures, and close correspondence was found.