27ps DFT Molecular Dynamics Simulation of a-maltose: A Reduced Basis Set Study.

Authors: Schnupf, Udo; Willett, Julious; Momany, Frank

Submitted to: Journal of Computational Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/3/2009
Publication Date: 12/29/2009
Citation: Schnupf, U., Willett, J.L., Momany, F.A. 2009. 27ps DFT Molecular Dynamics Simulation of a-maltose: A Reduced Basis Set Study.. Journal of Computational Chemistry.

Interpretive Summary: This computational study was carried out to better understand the flexibility and structural organization of starch materials, and this understanding will help us develop new and more efficient design methods for chemical and physical modifications of starch or biopolymer blends. The expectation is that new biodegradable natural polymers with interesting physical properties will be discovered using this data. These results are important to industries developing new biodegradable materials and to other computational and laboratory scientists working on simulation of starch materials and design of biological copolymers. Maltose is a disaccharide composed of two glucose residues separated by a glycosidic bond. It is a structural unit of starch polymers and an important model for amylose and amylopectin polymers, the main structural components of starch. In this work, a new and more rapid method of computing advanced quantum based molecular dynamics is developed. Molecular dynamics allows the study of molecules at room temperature, and is important for the understanding of the vibrational and structural landscape of carbohydrates in solution. Understanding the shape and conformational properties of this model carbohydrate as it vibrates around its equilibrium solution structure, allows interpretation of many important chemical and structural properties. For example, as the molecule changes its shape, some rarely observed structural features that help in the understanding of enzymatic cleavage occurs. That is, transient transition state geometries are found in this very long simulation, which would never be discovered by optimization studies. Advances in both computing software and hardware, combined with advances in the quantum mechanics regimen, allowed the long simulation described here. The current work reduces the dynamics simulation times by about a factor of ten, and reduces the memory requirements allowing the study of much larger molecular systems.

Technical Abstract: DFT molecular dynamics simulations are time intensive when carried out on carbohydrates such as alpha-maltose, requiring up to three or more weeks on a fast 16-processor computer to obtain just 5ps of constant energy dynamics. In a recent publication [1] forces for dynamics were generated from B3LYP/6-31+G* electronic structure calculations. The implicit solvent method COSMO was applied to simulate the solution environment. Here we present a modification of the DFT method that keeps the critical aspects of the larger basis set (B3LYP/6-31+G*) while allowing the less-essential atom interactions to be calculated using a smaller basis set, thus allowing for faster completion without sacrificing the interactions dictating the hydrogen bonding networks in the alpha-maltose carbohydrate. In previous studies, the gg’-gg-c solvated form quickly converged to the ‘r’ form during a 5 ps dynamics run. This important conformational transition is tested by carrying out a long 27ps simulation, starting from the ‘c’ form. The trend for the ‘r’ conformer to be most stable during dynamics when fully solvated, is confirmed, resulting in ~20/80% c/r population. Other features of interest include the hydroxyl rotamer populations and the hydroxymethyl O-H rotations. The study shows that considerable molecular end effects are important, the reducing end being fairly stable, the O6-H pointing at the O5’, while the non-reducing end moves freely to take on different conformations. Some “kink” and transition state forms are populated during the simulation. The average H1---H4’ distance of 2.28Å confirms that the syn form is the primary glycosidic conformation, while the average C1-O1-C4’ bond angle was 118.8o, in excellent agreement with experimental values. The length of this simulation allowed the evaluation of vibrational frequencies by Fourier transform of the velocity correlation function, taken from different time segments along the simulation path. From this one observes the frequency profile changes that occur with simulation time.