Abstract We present a CHARMM Carbohydrate Solution Force Field (CSFF) suitable for nanosecond molecular dynamics computer simulations. The force field was derived from recently published sugar parameter set. 1 Dihedral angle parameters the primary alcohol as well secondary hydroxyl groups were adjusted. Free energy profiles of hydroxymethyl group two monosaccharides (β‐ D ‐glucose and β‐ ‐galactose) calculated using new set compared with similar fields. Equilibrium rotamer populations...

Several blood‐feeding organisms, including the malaria parasite detoxify haem released from host haemoglobin by conversion to insoluble crystalline ferriprotoporphyrin IX dimer known as haemozoin. To date mechanism of haemozoin formation has remained unknown, although lipids or proteins have been suggested catalyse its formation. We found that β‐haematin (synthetic haemozoin) forms rapidly under physiologically realistic conditions near octanol/water, pentanol/water and lipid/water...

The puckered conformations of furanose and pyranose carbohydrate rings are central to analyzing the action enzymes on carbohydrates. Enzyme reaction mechanisms generally inaccessible experiments so have become focus QM(semiempirical)/MM simulations. We show that complete free energy puckering is required evaluate accuracy semiempirical methods used study reactions involving Interestingly, we find reducing space lower dimensions results in near meaningless minimum pathways. analyze pucker...

Abstract Aberrant glycosylation in tumours stem from altered glycosyltransferase (GT) gene expression but can the profiles of these signature genes be used to classify cancer types and lead subtype discovery? The differential structural changes cellular glycan structures are predominantly regulated by patterns GT a hallmark neoplastic cell metamorphoses. We found that 210 taken 1893 patient samples Cancer Genome Atlas (TCGA) microarray data able six cancers; breast, ovarian, glioblastoma,...

Analyses of trajectories generated in molecular dynamics (MD) computer simulations and pulse-field-gradient spin−echo nuclear magnetic resonance (PGSE NMR) experiments were used to investigate the origin anomalous solubility β-cyclodextrin (CD) water. The β-CD (seven glucose units) is 1 order magnitude lower compared with α- γ-CDs, which comprise six eight residues, respectively. translational diffusion coefficients derived from NMR MD are good agreement reveal a small but significant...

Abstract The approach used to calculate the two‐electron integral by many electronic structure packages including generalized atomic and molecular system‐UK has been designed for CPU‐based compute units. We redesigned algorithm acceleration on a graphical processing unit (GPU). report strategy illustrate it (ss|ss) type integrals. This is general Fortran‐based codes uses Accelerator compiler from Portland Group International GPU‐based accelerators Nvidia. evaluation of integrals within...

We have analyzed a set of molecular dynamics (MD) trajectories maltose in vacuum and water for solute imposed structuring on the solvent. To do this, we used novel technique to calculate probability densities locate areas which solvent is most populated solution. found that only layer within first hydration shell has density 50% greater than bulk water. On investigating this using Voronoi polyhedra (VP) analysis it was seen waters adjacent hydrophobic (CH CH2) groups are more structured...

Although the conformational preferences in glucose and galactose have been studied since early 1970s, only recently hydroxymethyl populations resolved by combining 3JHH 2JHH NMR coupling data using a modified Karplus equation. A preference for gauche conformations is observed monosaccharides, but reasons this are not understood. We calculated free energy of rotation profiles primary alcohols semiempirical description monosaccharides QM/MM simulations. From we excellent agreement between our...

Glycosylation of cellobiose hydrolase I (CBHI), is a key step in the processing and degradation cellulose. Here pathways barriers reaction are explored using free energy from adaptive coordinate forces (FEARCF) dynamics method coupled with SCC-DFTB/MM. In many respects CBHI follows expected general GH7 family mechanism that involves Glu-X-Asp-X-X-Glu motif. However, critical electronic conformational details, previously not known, were discovered through our computations. The central feature...

Molecular dynamics simulations employing adaptive umbrella sampling have been used to calculate the Ramachandran conformational potential of mean force in aqueous (TIP3P) solution for α(1→4)-linked dimer d-xylopyranose (4-O-α-d-xylopyranosyl-α-d-xylopyranose), a pentose analogue maltose and useful general model effects solvent structuring upon biopolymer hydration. The vacuum adiabatic energy map this molecule closely resembles that maltose, but pmf is quite different, with one principal...

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

Previously an adaptive reaction coordinate force biasing method based on probability distributions has been used to calculate the free energy of conformation, configuration and chemical reactions. This recently generalised perform calculations multidimensional coordinates. paper presents details this method, termed Free Energies from Adaptive Reaction Coordinate Forces (FEARCF). The efficiency sampling is demonstrated by applying it problem many characteristic pucker conformations a...

Understanding carbohydrate ring pucker is critical to rational design in materials and pharmaceuticals. Recently we have generalized our adaptive reaction coordinate force biasing method perform calculations on multidimensional coordinates. We termed this the Free Energies from Adaptive Reaction Coordinate Forces (FEARCF) method. Using FEARCF SCC-DFTB QM/MM non-Boltzmann simulations, are able calculate free energies of conformation. Here apply six-membered glucopyranose located an...

A semiempirical method based on the AM1/d Hamiltonian is introduced to model chemical glycobiological systems. We included in parameter training set glycans and environment often found about them glycoenzymes. Starting with RM1 AM1/d-PhoT models we optimized H, C, N, O, P atomic parameters targeting best performing molecular properties that contribute enzyme catalyzed glycan reaction mechanisms. The comprising glycans, amino acids, phosphates small organic systems was used derive reproduce...

<title>Abstract</title> Peptide O-glycosylation relies on the coordinated action of glycosyltransferases (GTs) within endoplasmic reticulum (ER) and Golgi apparatus. An in vitro one-pot synthetic biology approach was developed to investigate specificity kinetics GT O-GalNAc glycosylation that leads tumor antigen glycoforms mucin 1 (MUC1). The focus is experimentally simulate divergent pathways lead synthesis cancer-associated antigens (Tn, T) their sialylated derivatives. First, biosynthetic...

Aberrant O-glycosylation of mucin type glycopeptide 1 (MUC1) is implicated in cancerous cellular processes involving the manipulation immune response to favour tumour growth and metastasis. There an unmet need for systems glycobiology models probe relationship between MUC1 cells within microenvironment. We expand on sparsely understood cell interactions by building a complete model that combines glycosylation network with downstream biological networks. An ordinary differential...

We report the results of molecular dynamics (MD) simulations compared with NMR relaxation experiments for maltose and isomaltose. The (Φ,Ψ) adiabatic map shows a single principal energy well, while (Φ,Ψ,Ω) isomaltose reveals multiple low minima separated by significant barriers (9 kcal/mol) in some cases. greater accessible conformational space α(1→6) linkage appears to make it more flexible as α(1→4) linkage, especially presence water. Correlation times glycosidic dihedral angle...

Abstract We describe the implementation of an adaptive umbrella sampling method, making use weighted histogram analysis for computing multidimensional potential mean force chemical reaction in solution. The approach is illustrated by investigating effect aqueous solution on free energy surface proton transfer [H 3 N—H—NH ] + using a combined quantum mechanical and molecular AM1/TIP3P potential. © 2003 Wiley Periodicals, Inc. J Comput Chem 24: 1775–1781,

The two-dimensional melting transition of charged polystyrene spheres in aqueous colloidal suspension has been studied by molecular dynamics simulation a screened Coulomb system. Some central predictions the Kosterlitz–Thouless–Halperin–Nelson–Young theory defect-mediated are confirmed, such as an apparent divergence correlation lengths for translational and bond-orientational order at different thermodynamic state points, but there also that violated. defect topology is very complex, with...

ProtoCaller is a Python library distributed through Anaconda which automates relative protein–ligand binding free energy calculations in GROMACS. It links number of popular specialized tools used to perform protein setup and parametrization, such as PDB2PQR, Modeller, AmberTools. supports commonly AMBER force fields with additional cofactor parameters, AM1-BCC derive ligand charges. also comes an extensive PDB parser, enhanced maximum common substructure algorithm providing improved...

We studied the structure and conformation of organic organochromium poly(benzylphenyl ether) dendrimers (PBPE dendrimers) via atomistic molecular dynamics computer simulations. The results our computational investigations show that metal carbonyl centers are available to participate in chemical reactions. When a course-grain simulation study by Murat Grest1 were used, this conclusion was valid for all solvent conditions. terminal groups both smaller than generation 3 (gmax ≤ 3) undergo...

We construct force fields suited for the study of three platinum group metals (PGM) as chloranions in aqueous solution from quantum chemical computations and report experimental data. Density functional theory (DFT) using local density approximation (LDA), well extended basis sets that incorporate relativistic corrections transition metal atoms, has been used to obtain equilibrium geometries, harmonic vibrational frequencies, atomic charges complexes. found DFT calculations...

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 ab initio quantum calculations (Lienke, A.; Klatt, G.; Robinson, D.; Koch, K. R.; Naidoo, J. Inorg.Chem. 2001, 40, 2352-2357) to investigate the nature of hydration about simple platinum group metal chloro complexes ([PtCl(6)](2-), [RhCl(6)](3-), [PtCl(4)](2-),...