Biomedical subjects

Kevin J Naidoo

Publications and source records attributed to Kevin J Naidoo.

8 recordsLinked to original sources

PubMed2006

Haemozoin (beta-haematin) biomineralization occurs by self-assembly near the lipid/water interface.

Several blood-feeding organisms, including the malaria parasite detoxify haem released from host haemoglobin by conversion to the insoluble crystalline ferriprotoporphyrin IX dimer known as haemozoin. To date the mechanism of haemozoin formation has remained unknown, although lipids or proteins have been suggested to catalyse its formation. We have found that beta-haematin (synthetic haemozoin) forms rapidly under physiologically realistic conditions near octanol/water, pentanol/water and lipid/water interfaces. Molecular dynamics simulations show that a precursor of the haemozoin dimer forms spontaneously in the absence of the competing hydrogen bonds of water, demonstrating that this substance probably self-assembles near a lipid/water interface in vivo.

Animals↗

PubMed2005

Free energy surfaces for the alpha(1 --> 4)-glycosidic linkage: implications for polysaccharide solution structure and dynamics.

We present a potential of mean force surface for rotation about phi and psi dihedral angles of the alpha(1 --> 4)-glycosidic linkage in the maltose disaccharide (4-O-alpha-d-glucopyranosyl-d-glucopyranose) in aqueous solution. Comparison of the vacuum and solution free energy surfaces for maltose shows the principal effects of water to be an increase in the rotational freedom of the alpha(1 --> 4) linkage brought about by lowering the energy barrier for syn to anti conformational changes as well as expansion of the range of low-energy phi,psi conformations. This free energy analysis thus provides a thermodynamic and conformational rationale for the effects of water on alpha(1 --> 4)-linked polysaccharides and carbohydrate glasses.

Algorithms↗

PubMed2005

Ramachandran free-energy surfaces for disaccharides: trehalose, a case study.

We present calculated potential of mean force surfaces for rotation about phi, psi dihedral angles of the alpha(1<-->1)alpha-glycosidic linkage in the disaccharide trehalose (alpha-D-Glc-(1<-->1)-alpha-D-Glc) in both vacuum and aqueous solution. The effects of aqueous solvation upon the alpha(1<-->1)alpha-glycosidic linkage are investigated through comparison of the vacuum and aqueous solution free-energy surfaces. These surfaces reveal that trehalose is restricted to a single minimum-energy conformation in both vacuum and solution. The exceptional rigidity of this disaccharide in solution may provide a molecular rationale for the antidesiccant properties of trehalose glasses.

Carbohydrate Conformation↗

PubMed2005

Glycosidic linkage rotations determine amylose stretching mechanism.

The primary mechanism for relieving tensile strain in alpha-linked polysaccharides (e.g., [alpha-d-Glc-(1-->4)alpha-d-Glc]n) is achieved by complex rotations of the glycosidic linkages. This is shown through computer simulations of atomic force microscopy stretching experiments in combination with free energy calculations of the unfolding pattern for amylose. The experimental force-extension curve is reproduced and analyzed to reveal that the chair-to-boat conversions play a smaller role than previously proposed.

Amylose↗

PubMed2003

Implementation of an adaptive umbrella sampling method for the calculation of multidimensional potential of mean force of chemical reactions in solution.

We describe the implementation of an adaptive umbrella sampling method, making use of the weighted histogram analysis method, for computing multidimensional potential of mean force for chemical reaction in solution. The approach is illustrated by investigating the effect of aqueous solution on the free energy surface for the proton transfer reaction of [H(3)N-H-NH(3)](+) using a combined quantum mechanical and molecular mechanical AM1/TIP3P potential.

Mathematical Computing↗

PubMed2003

Contact ion pair between Na+ and PtCl(6)(2-) favored in methanol.

Ion-pair formation between a Na+ cation and the [PtCl62-] anion in methanol is observed from195Pt NMR chemical shift trends as well as from molecular dynamics computer simulations. Free energy of association calculations reveal that contact ion pairs (CIPs) are the most favored configuration in methanol, followed by solvent shared ion pairs (SSHIPs). By contrast, such ion-pair formation is not observed for comparable solutions in water.

Journal Article↗

PubMed2002

Geometric hydration shells for anionic platinum group metal chloro complexes.

Solvation shells surrounding complex inorganic anions have not been extensively studied and are often mentioned with an amorphous picture in mind. We use a computational model previously validated against experimental results and ab initio quantum calculations (Lienke, A.; Klatt, G.; Robinson, D.; Koch, K. R.; Naidoo, K. J. Inorg.Chem. 2001, 40, 2352-2357) to investigate the nature of the hydration shells about simple platinum group metal chloro complexes ([PtCl(6)](2-), [RhCl(6)](3-), [PtCl(4)](2-), and [PdCl(4)](2-)). Our simulations show that the hydration shells surrounding these complexes are symmetric and take on familiar geometric forms. We find that only the [RhCl(6)](3-) complex has a clearly defined second hydration shell while the [PtCl(6)](2-), [PtCl(4)](2-), and [PdCl(4)](2-) second hydration shells are more diffuse.

Journal Article↗

PubMed2002

Carbohydrate solution simulations: producing a force field with experimentally consistent primary alcohol rotational frequencies and populations.

We present a CHARMM Carbohydrate Solution Force Field (CSFF) suitable for nanosecond molecular dynamics computer simulations. The force field was derived from a recently published sugar parameter set.1 Dihedral angle parameters for the primary alcohol as well as the secondary hydroxyl groups were adjusted. Free energy profiles of the hydroxymethyl group for two monosaccharides (beta-D-glucose and beta-D-galactose) were calculated using the new parameter set and compared with similar force fields. Equilibrium rotamer populations obtained from the CSFF are in excellent agreement with NMR data (glucose gg:gt:tg approximately 66:33:1 and galactose gg:gt:tg approximately 4:75:21). In addition, the primary alcohol rotational frequency is on the nanosecond time scale, which conforms to experimental observations. Equilibrium population distributions of the primary alcohol conformers for glucose and galactose are reached within 10 nanoseconds of molecular dynamics simulations. In addition, gas phase vibrational frequencies computed for beta-D-glucose using this force field compare well with experimental frequencies. Carbohydrate parameter sets that produce both conformational energies and rotational frequencies for the pyranose primary alcohol group that are consistent with experimental observations should allow for increased accuracy in modeling the flexibility of biologically important (1-6)-linked saccharides in solution.

Alcohols↗