Unravelling interactions between active site residues and DMAP in the initial steps of prenylated flavin mononucleotide biosynthesis catalyzed by PaUbiX.

Background: Prenylated flavin mononucleotide (prFMN) is a recently discovered, heavily modified flavin compound. It is the only known cofactor that enables enzymatic 1,3-dipolar cycloaddition reactions. It is produced by enzymes from the UbiX family, from flavin mononucleotide and either dimethylallyl mono- or diphosphate.

Seeking the Source of Catalytic Efficiency of Lindane Dehydrochlorinase, LinA.

Herein we present the results of an in-depth simulation study of LinA and its two variants. In our analysis, we combined the exploration of protein conformational dynamics with and without bound substrates (hexachlorocyclohexane (HCH) isomers) performed using molecular dynamics simulation followed by the extraction of the most frequently visited conformations and their characteristics with a detailed description of the interactions taking place in the active site between the respective HCH molecule and the first shell residues by using symmetry-adapted perturbation theory (SAPT) calculations. A detailed investigation of the conformational space of LinA substates has been accompanied by description of enzymatic catalytic steps carried out using a hybrid quantum mechanics/molecular mechanics (QM/MM) potential along with the computation of the potential of mean force (PMF) to estimate the free energy barriers for the studied transformations: dehydrochlorination of γ-, (-)-α-, and (+)-α-HCH by LinA-type I and -type II variants.

Influence of short peptides with aromatic amino acid residues on aggregation properties of serum amyloid A and its fragments.

Serum amyloid A variant 1.1 (SAA1.1) is an acute phase protein.

MDMS: Software Facilitating Performing Molecular Dynamics Simulations.

Molecular Dynamics Made Simple (MDMS) is software that facilitates performing molecular dynamics (MD) simulations of solvated protein/protein-ligand complexes with Amber, one of the most popular MD codes. It guides users through the whole process of running MD starting with choosing a protein structure, preparing the model, parametrization of the system, establishing parameters for controlling MD, and finally running simulations. By accommodating every step required for running MD, this software ensures that the simulations performed by a user will provide as realistic insight as it is possible.

Ligand-Driven Conformational Dynamics Influences Selectivity of UbiX.

Up until now, it has remained elusive as to why the flavin prenyltransferase UbiX requires dimethylallyl monophosphate (DMAP) as one of its cosubstrates instead of dimethylallyl pyrophosphate (DMAPP), even though the former is not used in metabolic pathways, while the latter is a common isoprenoid precursor. Herein, mainly on the basis of molecular dynamics (MD) simulations, we demonstrate that the selectivity of UbiX may be governed by its conformational dynamics. The hydrogen-bonding network of UbiX does not facilitate a proper encompassing of DMAPP.

A Benchmark Study of Kinetic Isotope Effects and Barrier Heights for the Finkelstein Reaction.

Herein, we present a combined (experimental and computational) study of the Finkelstein reaction in condensed phase, where bromine is substituted by iodine in 2-bromoethylbenzene, in the presence of either acetone or acetonitrile as a solvent. Performance of various density functional theory and ab initio methods were tested for reaction barrier heights as well as for bromine and carbon kinetic isotope effects (KIEs). Two different implicit solvation models were examined (PCM and SMD).