Computational investigation of impact of Pb(II) and Ni(II) ions on hUNG enzyme: insights from molecular dynamics simulations.

Human uracil DNA glycosylase (hUNG), a crucial player in the initiation of the base excision repair pathway, is susceptible to alterations in function and conformation induced by the accumulation of toxic metals. Despite the recognized impact of toxic metals on DNA repair enzymes, there exists a notable deficiency in theoretical investigations addressing this phenomenon. This study investigates the impact of toxic heavy metal ions, Pb(II) and Ni(II), on the stability of hUNG through molecular dynamics (MD) simulations.

Impact of Cd(II) on the stability of human uracil DNA glycosylase enzyme; an implication of molecular dynamics trajectories on stability analysis.

Uracil DNA glycosylase is a key enzyme that identifies and removes damaged bases from DNA in the base excision repair pathway. Experimentalists have identified the possibility of Cd(II) reducing the activity of human uracil DNA glycosylase (hUNG) by binding with the enzyme replacing the catalytic water molecule. The present study focus on the stability variation of the enzyme in the presence and absence of Cd(II) and confirms the reported results with the stability analysis done using molecular dynamic (MD) simulation trajectories.

Kirkwood-Buff-Derived Force Field for Peptides and Proteins: Philosophy and Development of KBFF20.

A new classical nonpolarizable force field, KBFF20, for the simulation of peptides and proteins is presented. The force field relies heavily on the use of Kirkwood-Buff theory to provide a comparison of simulated and experimental Kirkwood-Buff integrals for solutes containing the functional groups common in proteins, thus ensuring intermolecular interactions that provide a good balance between the peptide-peptide, peptide-solvent, and solvent-solvent distributions observed in solution mixtures. In this way, it differs significantly from other biomolecular force fields.

Cracking a cancer code histone deacetylation in epigenetic: the implication from molecular dynamics simulations on efficacy assessment of histone deacetylase inhibitors.

Epigenetic changes, histone acetylation and deacetylation in chromatin have been intensively studied due to their significance in regulating the gene expression. According to the type of tumor, the levels of histone deacetylases (HDAC) are varied. HDAC inhibitors are a new promising class of compounds that inhibit the proliferation of tumor cells.

Plausible compounds drawn from plants as curative agents for neurodegeneration: An in-silico approach.

Classification of chemical compounds of plants as a source of medicaments for neurodegenerative diseases through computer screening is an efficient process in drug discovery, in advance of laboratory testing and clinical trials. The onset of neurodegenerative disorders incarcerates both sufferers and their families mentally and financially. This investigation emphasises the search for potent compounds via a computational approach, as an initial path towards the treatment of the neurodegenerative diseases Alzheimer's (AD), Parkinson's (PD), prion, and Huntington's (HD) diseases.

Structure and Dynamics of Collagen Hydration Water from Molecular Dynamics Simulations: Implications of Temperature and Pressure.

Dynamics of water molecules in hydrated collagen plays an important role in determining the structural and functional properties of collagenous tissues. Experimental results suggest that collagen-bridging water molecules exhibit dynamic and thermodynamic properties of one-dimensional ice. However, molecular dynamics (MD) studies performed to date have failed to identify icelike water bridges.

Exploring the binding properties of agonists interacting with glucocorticoid receptor: an in silico approach.

The glucocorticoid receptors (GR) are members of the nuclear receptor superfamily that regulate growth, development, and many of the biological functions, including metabolism and inflammation, in a ligand dependent behavior. Thus, GRs are vital as therapeutic targets with steroid hormones and steroidal analogues, especially including the glucocorticoids. Studying the molecular mechanism of binding between GR and ligands is fundamentally important to develop applications in the pharmacological industry.

Development of an Information System of Structures and Force Field Parameters of Chemical Compounds from Sri Lankan Flora.

Background: Sri Lanka offers a huge diversity of flora with a large proportion of those being endemic to the island. Both the endemic and native plants species serve as a rich bank of phytochemicals.

Method: In this study, "Sri Lankan Flora" an online web-based information system of phytochemical compounds isolated from the flora of Sri Lanka was proposed.

Rotational-Diffusion Propagator of the Intramolecular Proton-Proton Vector in Liquid Water: A Molecular Dynamics Study.

The rotational motion of water molecules plays the dominant role in determining NMR spin-relaxation properties of liquid water and many biological tissues. The traditional theory of NMR spin relaxation predominantly uses the assumption that the reorientational dynamics of water molecules is described by a continuous-time rotational-diffusion random walk with a single rotational-diffusion coefficient. However, recent experimental and theoretical studies have demonstrated that water reorientation occurs by large, discrete angular jumps superimposed on a continuous-time rotational-diffusion process.

Theory and Simulation of Multicomponent Osmotic Systems.

Most cellular processes occur in systems containing a variety of components many of which are open to material exchange. However, computer simulations of biological systems are almost exclusively performed in systems closed to material exchange. In principle, the behavior of biomolecules in open and closed systems will be different.

Simulation of structural and functional properties of mevalonate diphosphate decarboxylase (MVD).

Mevalonate 5-diphosphate decarboxylase (MVD) is an important enzyme in the mevalonate pathway catalyzing the ATP-dependent decarboxylation of mevalonate 5-diphosphate (MDP) to yield isopentynyl diphosphate (IPP) which is an ubiquitous precursor for isoprenoids and sterols. Although there are studies to show the involvement of certain amino acid residues in MVD activity, the structure and the function of the active site is yet to be investigated. Therefore the objectives of this study were to elucidate the active site of Saccharomyces cerevisiae MVD (scMVD) using a molecular docking and simulation-based approach.

Recent applications of Kirkwood-Buff theory to biological systems.

The effect of cosolvents on biomolecular equilibria has traditionally been rationalized using simple binding models. More recently, a renewed interest in the use of Kirkwood-Buff (KB) theory to analyze solution mixtures has provided new information on the effects of osmolytes and denaturants and their interactions with biomolecules. Here we review the status of KB theory as applied to biological systems.

A Kirkwood-Buff derived force field for methanol and aqueous methanol solutions.

A force field for the simulation of methanol and aqueous methanol mixtures is presented. The force field was specifically designed to reproduce the experimental Kirkwood-Buff integrals as a function of methanol mole fraction, thereby ensuring a reasonable description of the methanol cosolvent and water solvent activities. Other thermodynamic and physical properties of pure methanol and aqueous methanol solutions, including the density, enthalpy of mixing, translational diffusion constants, compressibility, thermal expansion, and dielectric properties, were also well reproduced.

A Kirkwood-Buff derived force field for the simulation of aqueous guanidinium chloride solutions.

A force field for the simulation of aqueous guanidinium chloride solutions is presented. The force field was parametrized to reproduce the experimental density and Kirkwood-Buff integrals as a function of composition. Consequently, a reasonable description of the salt activity is obtained.