Biomedical subjects

J L Willett

Publications and source records attributed to J L Willett.

12 recordsLinked to original sources

PubMed2006

DFT study of alpha- and beta-D-allopyranose at the B3LYP/6-311++G ** level of theory.

One hundred and two conformations of alpha- and beta-D-allopyranose, the C-3 substituted epimer of glucopyranose, were geometry optimized using the density functional, B3LYP, and the basis set, 6-311++G **. Full geometry optimization was performed on different ring geometries and on the hydroxymethyl rotamers (gg/gt/tg). Analytically derived Hessians were used to calculate zero point energy, enthalpy, and entropy. The lowest energy and free energy conformation found is the alpha-tg(g-)-4C1-c conformation, which is only slightly higher in electronic (approximately 0.2 kcal/mol) and free energy than the lowest energy alpha-D-glucopyranose. The in vacuo calculations showed a small (approximately 0.3 kcal/mol) energetic preference for the alpha- over the beta-anomer for allopyranose in the 4C1 conformation, whereas in the 1C4 conformation a considerable (approximately 1.6 kcal/mol) energetic preference for the beta- over the alpha-anomer for allopyranose was encountered. The results are compared to previous aldohexose calculations in vacuo. Boat and skew forms were found that remained stable upon gradient optimization although many starting boat conformations moved to other skew forms upon optimization. As found for glucose, mannose, and galactose the orientation and interaction of the hydroxyl groups make the most significant contributions to the conformation/energy relationship in vacuo. A comparison of different basis sets and density functionals is made in the Discussion section, confirming the appropriateness of the level of theory used here.

Carbohydrate Conformation↗

PubMed2006

DFT study of alpha- and beta-D-galactopyranose at the B3LYP/6-311++G** level of theory.

Forty-one conformations of alpha- and beta-d-galactopyranose were geometry optimized using the B3LYP density functional and 6-311++G** basis set. Full geometry optimization was performed on different ring geometries and different hydroxymethyl rotamers (gg/gt/tg). Analytically derived Hessians were used to calculate zero point energy, enthalpy, and entropy. The lowest energy and free-energy conformation found is the alpha-gg-(4)C(1)-c chair conformation, which is of lower electronic and free energy than the lowest energy alpha-d-glucopyranose conformer because of favorable hydrogen-bonding interactions. The in vacuo calculations showed considerable ( approximately 2.2kcal/mol) energetic preference for the alpha over the beta anomer for galactopyranose in both the (4)C(1) and (1)C(4) chair conformations. Results are compared to glucopyranose and mannopyranose calculations in vacuo. Boat and skew-boat forms were found that remained stable upon gradient optimization, although many starting conformations moved to other boat forms upon optimization. As with glucopyranose and mannopyranose, the orientation and interaction of the hydroxyl groups make the most significant contributions to the conformation-energy relationship in vacuo.

Carbohydrate Conformation↗

PubMed2005

B3LYP/6-311++G** geometry-optimization study of pentahydrates of alpha- and beta-D-glucopyranose.

Five water molecules were placed in 37 different configurations around alpha- and beta-D-glucopyranose in the gt, gg, and tg conformational states, and the glucose-water complexes were geometry optimized using density functionals at the B3LYP/6-311++G** level of theory. The five water molecules were organized in space and energy minimized using an empirical potential, AMB02C, and then further geometry optimized using DFT algorithms to minimum energy positions. Electronic energy, zero point vibrational energy, enthalpy, entropy, stress energy on glucose and the water cluster, hydrogen-bond energy, and relative free energy were obtained for each configuration using thermodynamic procedures and an analytical Hessian program. The lowest energy complex was that of a clustering of water molecules around the 1- and 6-hydroxyl positions of the beta-gt anomer. Configurations in which the water molecules created a favorable network completely around and under glucose were found to have low energy for both alpha and beta anomers. Calculation of the alpha/beta anomeric ratio using the zero point corrected energy gave, approximately 32/68%, highly favoring the beta anomer in agreement with the experimental approximately 36/64% value. This ratio is better than the approximately 50/50% ratio found in our previous monohydrate study. An approximate hydroxymethyl population was obtained by noting average relative energies among the three conformational states, gt, gg, and tg. In the beta anomer complexes the gt conformation was favored over the gg state, while in the alpha anomer complexes the gg state was favored over the gt conformation, with the tg conformations all being of higher energy making little or no contribution to the rotamer population. Some geometry variances, found between glucose in vacuo and glucose after interaction with water molecules, are described and account for some observed C-5-C-6 bond length anomalies reported by us previously for the vacuum glucose structures.

Glucose↗

PubMed2005

DFT study of alpha- and beta-D-mannopyranose at the B3LYP/6-311++G** level.

Thirty-five conformations of alpha- and beta-d-mannopyranose, the C-2 substituted epimer of glucopyranose, were geometry optimized using the density functional (B3LYP), and basis set (6-311++G**). Full geometry optimization was performed on the hydroxymethyl rotamers (gg/gt/tg) and an analytical hessian program was used to calculate the harmonic vibrational frequencies, zero point energy, enthalpy, and entropy. The lowest energy conformation investigated is the beta-tg in the (4)C(1) chair conformation. The in vacuo calculations showed little energetic preference for either the alpha or beta anomer for mannopyranose in the (4)C(1) chair conformation. Results are compared to similar glucopyranose calculations in vacuo where the alpha anomer is approximately 1kcal/mol lower in electronic energy than the beta anomer. In the case of the generally higher energy (1)C(4) chair conformations, one low-energy, low-entropy beta-gg-(1)C(4) chair conformation was identified that is within approximately 1.4kcal/mol of the lowest energy (4)C(1) conformation of mannopyranose. Other (1)C(4) chair conformations in our investigation are approximately 2.9-7.9kcal/mol higher in overall energy. Many of the (3,O)B, B(3,O), (1,4)B, and B(1,4) boat forms passed through transitions without barriers to (1)S(3), (5)S(1), (1)S(5) skew forms with energies between approximately 3.6 and 8.9kcal/mol higher in energy than the lowest energy conformation of mannopyranose. Boat forms were found that remained stable upon gradient optimization. As with glucopyranose, the orientation and interaction of the hydroxy groups make a significant contribution to the conformation/energy relationship in vacuo.

Carbohydrate Conformation↗

PubMed2004

B3LYP/6-311++G** study of monohydrates of alpha- and beta-D-glucopyranose: hydrogen bonding, stress energies, and effect of hydration on internal coordinates.

Twenty-six monohydrates of alpha- and beta-D-glucopyranose were studied using gradient methods at the B3LYP/6-311++G** level of theory. Geometry optimization was carried out with the water molecules at different configurations around the glucose molecule. A new nomenclature for hydrated carbohydrates was developed to describe the water configurations. Zero-point vibrational energy, enthalpy, entropy, and relative free energy were obtained using the harmonic approximation. Hydrogen-bond energies for the monohydrates range from approximately -5 to -12 kcal/mol, and the average relative free energy is approximately 5 kcal/mol. The 1-hydroxy position is the most energetically favored site for hydration, and the region between the two and three positions is the next-most favored site. A water molecule approaching alpha-D-glucose between the 1- and 2-hydroxy positions pulls the 2-hydroxyl hydrogen atom away from the 1-hydroxy oxygen atom, thus increasing the hydrogen-bond length and also increasing the alpha-D-glucose energy. The increase in energy that occurs with a similar interaction on the beta-anomer is much less effective since the hydrogen bond is much longer. Using the calculated free energies of all 26 configurations, the anomer population (alpha/beta) increases in the beta-anomer population relative to the in vacuo case by approximately 10% at the expense of the alpha-anomer, giving an (alpha/beta) ratio of approximately 50/50. This result arises from entropy contributions favoring the beta-anomer more than the alpha-anomer. From analysis of donor and acceptor hydrogen-bond lengths, excellent correlation is found between the DFT calculated distances and those taken from carbohydrate structures in the Cambridge Crystallographic Data Bank.

Carbohydrate Conformation↗

PubMed2004

B3LYP/6-311++G** study of alpha- and beta-D-glucopyranose and 1,5-anhydro-D-glucitol: 4C1 and 1C4 chairs, (3,O)B and B(3,O) boats, and skew-boat conformations.

Geometry optimization, at the B3LYP/6-311++G** level of theory, was carried out on 4C1 and 1C4 chairs, (3,O)B and B(3,O) boats, and skew-boat conformations of alpha- and beta-D-glucopyranose. Similar calculations on 1,5-anhydro-D-glucitol allowed examination of the effect of removal of the 1-hydroxy group on the energy preference of the hydroxymethyl rotamers. Stable minimum energy boat conformers of glucose were found, as were stable skew boats, all having energies ranging from approximately 4-15 kcal/mol above the global energy 4C1 chair conformation. The 1C4 chair electronic energies were approximately 5-10 kcal/mol higher than the 4C1 chair, with the 1C4 alpha-anomers being lower in energy than the beta-anomers. Zero-point energy, enthalpy, entropy, and relative Gibbs free energies are reported at the harmonic level of theory. The alpha-anomer 4C1 chair conformations were found to be approximately 1 kcal/mol lower in electronic energy than the beta-anomers. The hydroxymethyl gt conformation was of lowest electronic energy for both the alpha- and beta-anomers. The glucose alpha/beta anomer ratio calculated from the relative free energies is 63/37%. From a numerical Hessian calculation, the tg conformations were found to be approximately 0.4-0.7 kcal/mol higher in relative free energy than the gg or gt conformers. Transition-state barriers to rotation about the C-5-C-6 bond were calculated for each glucose anomer with resulting barriers to rotation of approximately 3.7-5.8 kcal/mol. No energy barrier was found for the path between the alpha-gt and alpha-gg B(3,O) boat forms and the equivalent 4C1 chair conformations. The alpha-tg conformation has an energy minimum in the 1S3 twist form. Other boat and skew-boat forms are described. The beta-anomer boats retained their starting conformations, with the exception of the beta-tg-(3,O)B boat that moved to a skew form upon optimization.

Carbohydrate Conformation↗

PubMed2002

A spectrophotometric assay for feruloyl esterases.

We have developed a spectrophotometric assay for the quantitative determination of feruloyl esterase activity based on release of 4-nitrophenol from a novel substrate, 4-nitrophenyl ferulate in an emulsion of Triton X-100 in aqueous buffer solution. The release of 4-nitrophenol was linear with reaction time at an early stage of the reaction with various esterase preparations. The method proposed here is accurate, rapid, and easy to perform.

Carboxylic Ester Hydrolases↗

PubMed2002

Molecular dynamics calculations on amylose fragments. I. Glass transition temperatures of maltodecaose at 1, 5, 10, and 15.8% hydration.

Molecular dynamics simulations (NPT ensembles, 1 atm) using the all atom force field AMB99C (F. A. Momany and J. L. Willett, Carbohydrate Research, Vol. 326, pp 194-209 and 210-226), are applied to a periodic cell containing ten maltodecaose fragments and TIP3P water molecules. Simulations were carried out at 25 K intervals over a range of temperatures above and below the expected glass transition temperature, T(g), for different water concentrations. The amorphous cell was constructed through successive dynamic equilibration steps at temperatures above T(g) and the temperature lowered until several points of reduced slope (1/T vs volume) were obtained. This procedure was carried out at each hydration level. Each dynamics simulation was continued until the volume remained constant without up or down drift for at least the last 100 ps. For a given temperature, most simulations required 400-600 ps to reach an equilibrium state, but longer times were necessary as the amount of water in the cell was reduced. A total of more than 30 ns of simulations were required for the complete study. The T(g) for each hydrated cell was taken as that point at which a discontinuity in slope of the volume (V), potential energy (PE), or density (rho) vs 1/T was observed. The average calculated T(g) values were 311, 337, 386, and 477 K for hydration levels of 15.8, 10, 5, and 1%, respectively, in generally good agreement with experimental values. The T(g) for anhydrous amylose is above the decomposition temperature for carbohydrates and so cannot be easily measured. However, it has also been difficult to obtain a value of T(g) for anhydrous amylose using simulation methods. Other molecular parameters such as end-to-end distances, mean square distributions, and pair distributions are discussed.

Amylose↗

PubMed2001

Improved antimicrobial activity of nisin-incorporated polymer films by formulation change and addition of food grade chelator.

AIMS: The following polymers were developed: polyethylene (PE), a PE and polyethylene oxide (70% PE and 30% PEO; PE + PEO) blend, PE and nisin (PE + nisin), PE, nisin, and EDTA (PE + nisin + EDTA), and PE + PEO with nisin (PE + PEO + nisin). METHODS AND RESULTS: Of the polymers tested, PE and PE + PEO did not exhibit any antimicrobial activity against Brochothrix thermosphacta (BT); however, PE + nisin, PE + nisin + EDTA, and PE + PEO + nisin did. Beef surfaces were experimentally inoculated with 3.50 log10 cfu/cm2 of BT, vacuum packaged with each of the five polymers, and held at 4 degrees C for 21 d. After 3 d at 4 degrees C, BT was reduced > 1.70 log(10) by PE + nisin and > 3.50 log(10) with PE + nisin + EDTA or PE + PEO + nisin. By 21 d at 4 degrees C, BT was reduced to 0.30 log(10) cfu/cm(2) when treated with PE + PEO + nisin. CONCLUSION: It appears that PE + PEO + nisin or PE + nisin + EDTA were more effective for reducing BT, as compared to polymers composed of PE + nisin. SIGNIFICANCE AND IMPACT OF THE STUDY: Nisin-incorporated polymers may control the growth of undesirable bacteria, thereby extending the shelf life and possibly enhancing the microbial safety of meats.

Anti-Bacterial Agents↗

PubMed2000

Computational studies on carbohydrates: in vacuo studies using a revised AMBER force field, AMB99C, designed for alpha-(1-->4) linkages.

Modifications to the AMBER force field [W.D. Cornell, P. Cieplak, C.I. Bayly, I.R. Gould, K. Merz, D.M. Ferguson, D.C. Spellmeyer, T. Fox, J.W. Caldwell, P.A. Kollman, J. Am. Chem. Soc., 117 (1995) 5179-5197] have been made to improve our ability to reproduce observed molecular properties of alpha-linked carbohydrates when calculated using empirical potential-energy functions. Molecular structures and energies obtained using gradient-optimized density functional methods with ab initio basis sets (B3LYP/6-31G*) on ten minimum-energy conformations of maltose [F.A. Momany, J.L. Willett, J. Comp. Chem., submitted for publication] were used to refine the empirical potentials. Molecular dynamics simulations on beta-maltose (i.e., the beta anomer of maltose), cyclohexamylose (alpha-cyclodextrin), cycloheptamylose (beta-cyclodextrin) and larger cyclomaltooligosaccharide structures were carried out and compared with experimental structural studies to test the new potentials. Ring-puckering potential during dynamics as well as conformational transitions to 'flipped' structures were examined. Results of the tests described here suggest that the revised AMBER parameters (AMB99C) are very good for computational studies of alpha-(1-->4)-linked carbohydrates.

Amylose↗

PubMed2000

Computational studies on carbohydrates: solvation studies on maltose and cyclomaltooligosaccharides (cyclodextrins) using a DFT/ab initio-derived empirical force field, AMB99C.

An empirical force field, denoted AMB99C, has been used to study molecular properties of alpha-(1-->4)-linked carbohydrates in solution. AMB99C was parameterized using structural and energetic parameters from density functional ab initio methodology. In this work we examine the solution behavior of the beta anomer of maltose and cyclohexa-, cyclohepta-, and cyclooctaamyloses (alpha-, beta-, and gamma-cyclodextrins or alpha-, beta-, and gamma-CDs, respectively), as well as of two larger (DP 10, epsilon-CD; DP 21) cyclomaltooligosaccharides, CA10 and CA21. Experimental data used for comparison purposes include X-ray structures, small-angle scattering radius of gyration values, NMR nuclear Overhauser enhancements (NOEs), and proton coupling constants. Molecular dynamics simulations were carried out using explicit water molecules (TIP3P) to establish equilibrium populations of conformations in solution, and these results are compared with other calculated values and a variety of experimental parameters, such as average H-1-H-4' distances between the rings in beta-maltose, and the primary hydroxyl groups' conformational populations. Medium-to-large cyclomaltooligosaccharide molecules were studied to test for glucose ring puckering and stability of kinked and 'flipped' conformations. The results of the solvation studies are in excellent agreement with experimental structural parameters.

Carbohydrate Conformation↗

PubMedDate not supplied

Solvent-free process to esterify polysaccharides.

A novel process for the preparation of acetates of polysaccharides is described herein. The process involves the acetylation of polysaccharides with acetic anhydride in the presence of iodine as a catalyst. No solvent is required to bring about the acetylation. The method is simple, rapid, and characterized by a high conversion ratio. Conversion of cellulose and starch into their corresponding acetate derivatives has been demonstrated.

Acetic Acid↗