A molecular dynamics simulation study of EthylChlorophyllide A molecules confined in a SiO2 nanoslit.

This paper investigates the dynamic behavior of EthylChlorophyllide A (EChlideA) molecules in a methanol solution confined within a 4 nm silica nanoslit, using molecular dynamics simulations over a duration of 1 ms. Three systems, containing 1, 2, and 4 solutes, were studied at 298 K. The results demonstrate that EChlideA molecules predominantly adsorb onto the silica surfaces, driven by specific interactions between chlorin ring's methyl group and the hydroxyl groups of the silica.

A molecular dynamics simulation study of glycine/serine octapeptides labeled with 2,3-diazabicyclo[2.2.2]oct-2-ene fluorophore.

The compound 2,3-diazabicyclo[2.2.2]oct-2-ene (DBO) is a versatile fluorophore widely used in Förster resonance energy transfer (FRET) spectroscopy studies due to its remarkable sensitivity, enabling precise donor-acceptor distance measurements, even for short peptides.

Modelling the adsorption of proteins to nanoparticles at the solid-liquid interface.

Hypothesis: We developed a geometrical model to determine the theoretical maximum number of proteins that can pack as a monolayer surrounding a spherical nanoparticle. We applied our new model to study the adsorption of receptor binding domain (RBD) of the SARS-CoV-2 spike protein to silica nanoparticles. Due to its abundance and extensive use in manufacturing, silica represents a reservoir where the virus can accumulate.

The Molecular Dynamics Simulation of Peptides on Gold Nanosurfaces.

This chapter contributes a short tutorial on the preparation of molecular dynamics (MD) simulations for a peptide in solution at the interface of an uncoated gold nanosurface. Specifically, the step-by-step procedure will give guidance to set up the simulation of a 16 amino acid long antimicrobial peptide on a gold layer using the program Gromacs for MD simulations.

Free Energy Profile of Domain Movement in Ligand-Free Citrate Synthase.

Citrate synthase plays a fundamental role in the metabolic cycle of the cell. Its catalytic mechanism is complex involving the binding of two substrates that cause a domain movement. In this paper, we used classical molecular dynamics simulations and umbrella-sampling simulations to determine the potential of mean force along a reaction coordinate for the domain movement in ligand-free citrate synthase from pig ( Sus scrofa).

Modular assembly of proteins on nanoparticles.

Generally, the high diversity of protein properties necessitates the development of unique nanoparticle bio-conjugation methods, optimized for each different protein. Here we describe a universal bio-conjugation approach which makes use of a new recombinant fusion protein combining two distinct domains. The N-terminal part is Glutathione S-Transferase (GST) from Schistosoma japonicum, for which we identify and characterize the remarkable ability to bind gold nanoparticles (GNPs) by forming gold-sulfur bonds (Au-S).

Adsorption mechanism of an antimicrobial peptide on carbonaceous surfaces: A molecular dynamics study.

Peptides are versatile molecules with applications spanning from biotechnology to nanomedicine. They exhibit a good capability to unbundle carbon nanotubes (CNT) by improving their solubility in water. Furthermore, they are a powerful drug delivery system since they can easily be uptaken by living cells, and their high surface-to-volume ratio facilitates the adsorption of molecules of different natures.

Molecular Properties of Astaxanthin in Water/Ethanol Solutions from Computer Simulations.

Astaxanthin (AXT) is a reference model of xanthophyll carotenoids, which is used in medicine and food industry, and has potential applications in nanotechnology. Because of its importance, there is a great interest in understanding its molecular properties and aggregation mechanism in water and mixed solvents. In this paper, we report a novel model of AXT for molecular dynamics simulation.

Strings-to-Rings Transition and Antiparallel Dipole Alignment in Two-Dimensional Methanols.

Structural order emerging in the liquid state necessitates a critical degree of anisotropy of the molecules. For example, liquid crystals and Langmuir monolayers require rod- or disc-shaped and long-chain amphiphilic molecules, respectively, to break the isotropic symmetry of liquids. In this Letter we present results from molecular dynamics simulations demonstrating that in two-dimensional liquids, a significantly smaller degree of anisotropy is sufficient to allow structural organization.

Unraveling Binding Effects of Cobalt(II) Sepulchrate with the Monooxygenase P450 BM-3 Heme Domain Using Molecular Dynamics Simulations.

One of the major limitations to exploit enzymes in industrial processes is their dependence on expensive reduction equivalents like NADPH to drive their catalytic cycle. Soluble electron-transfer (ET) mediators like cobalt(II) sepulchrate have been proposed as a cost-effective alternative to shuttle electrons between an inexpensive electron source and an enzyme's redox center. The interactions of these molecules with enzymes have not yet been elucidated at the molecular level.

Iterative key-residues interrogation of a phytase with thermostability increasing substitutions identified in directed evolution.

Bacterial phytases have attracted industrial interest as animal feed supplement due to their high activity and sufficient thermostability (required for feed pelleting). We devised an approach named KeySIDE,  an iterative Key-residues interrogation of the wild type with Substitutions Identified in Directed Evolution for improving Yersinia mollaretii phytase (Ymphytase) thermostability by combining key beneficial substitutions and elucidating their individual roles. Directed evolution yielded in a discovery of nine positions in Ymphytase and combined iteratively to identify key positions.

Structure, dynamics, and function of the monooxygenase P450 BM-3: insights from computer simulations studies.

The monooxygenase P450 BM-3 is a NADPH-dependent fatty acid hydroxylase enzyme isolated from soil bacterium Bacillus megaterium. As a pivotal member of cytochrome P450 superfamily, it has been intensely studied for the comprehension of structure-dynamics-function relationships in this class of enzymes. In addition, due to its peculiar properties, it is also a promising enzyme for biochemical and biomedical applications.

Cosolvent, ions, and temperature effects on the structural properties of Cecropin A-Magainin 2 hybrid peptide in solutions.

Antimicrobial peptides are promising alternative to traditional antibiotics and antitumor drugs for the battle against new antibiotic resistant bacteria strains and cancer maladies. The study of their structural and dynamics properties at physiological conditions can help to understand their stability, delivery mechanisms, and activity in the human body. In this article, we have used molecular dynamics simulations to study the effects of solvent environment, temperature, ions concentration, and peptide concentration on the structural properties of the antimicrobial hybrid peptide Cecropin A-Magainin 2.

The Mutagenesis Assistant Program.

Mutagenesis Assistant Program (MAP) is a web-based statistical tool to develop directed evolution strategies by investigating the consequences at the amino acid level of the mutational biases of random mutagenesis methods on any given gene. The latest development of the program, the MAP(2.0)3D server, correlates the generated amino acid substitution patterns of a specific random mutagenesis method to the sequence and structural information of the target protein.

Micellar drug nanocarriers and biomembranes: how do they interact?

Pluronic based formulations are among the most successful nanomedicines and block-copolymer micelles including drugs that are undergoing phase I/II studies as anticancer agents. Using coarse-grained models, molecular dynamics simulations of large-scale systems, modeling Pluronic micelles interacting with DPPC lipid bilayers, on the μs timescale have been performed. Simulations show, in agreement with experiments, the release of Pluronic chains from the micelle to the bilayer.

Insights on activity and stability of subtilisin E towards guanidinium chloride and sodium dodecylsulfate.

A subtilisin E variant (M4) showing high activity and resistance towards guanidinium chloride (GdmCl) and sodium dodecylsulfate (SDS) was previously identified after three rounds of directed evolution [Li et al., ChemBioChem 2012, 13(5), 691-699.].

Theoretical study of binding and permeation of ether-based polymers through interfaces.

We present a molecular dynamics simulation study on the interactions of poly(ethylene oxide) (PEO), poly(propylene oxide) (PPO), and their ABA-type block copolymer, poloxamers, at water/n-heptane and 1,2-dimyristoyl-sn-glycero-3-phospatidycholine (DMPC) lipid bilayer/water interfaces. The partition coefficients in water/1-octanol of the linear polyethers up to three monomers were calculated. The partition coefficients evidenced a higher hydrophobicity of the PPO in comparison to PEO.

Insight into the redox partner interaction mechanism in cytochrome P450BM-3 using molecular dynamics simulations.

Flavocytochrome P450BM-3 is a soluble bacterial reductase composed of two flavin (FAD/FMN) and one HEME domains. In this article, we have performed molecular dynamics simulations on both the isolated FMN and HEME domains and their crystallographic complex, with the aim to study their binding modes and to garner insight into the interdomain electron transfer (ET) mechanism. The results evidenced an interdomain conformational rearrangement that reduces the average distance between the FMN and HEME cofactors from 1.

MAP(2.0)3D: a sequence/structure based server for protein engineering.

The Mutagenesis Assistant Program (MAP) is a web-based tool to provide statistical analyses of the mutational biases of directed evolution experiments on amino acid substitution patterns. MAP analysis assists protein engineers in the benchmarking of random mutagenesis methods that generate single nucleotide mutations in a codon. Herein, we describe a completely renewed and improved version of the MAP server, the MAP(2.

P450 BM3 crystal structures reveal the role of the charged surface residue Lys/Arg184 in inversion of enantioselective styrene epoxidation.

Solved crystal structures of P450 BM3 variants in complex with styrene provide on the molecular level a first explanation of how a positively charged surface residue inverts the enantiopreference of styrene epoxidation. The obtained insights into productive and non-productive styrene binding modes deepened our understanding of enantioselective epoxidation with P450 BM3.

Interaction of Curcumin with PEO-PPO-PEO block copolymers: a molecular dynamics study.

Curcumin, a naturally occurring drug molecule, has been extensively investigated for its various potential usages in medicine. Its water insolubility and high metabolism rate require the use of drug delivery systems to make it effective in the human body. Among various types of nanocarriers, block copolymer based ones are the most effective.

Conformational Dynamics of the FMN-Binding Reductase Domain of Monooxygenase P450BM-3.

In the cytochrome P450BM-3, the flavin mononucleotide (FMN) binding domain is an intermediate electron donor between the flavin adenine dinucleotide (FAD) binding domain and the HEME domain. Experimental evidence has shown that different redox states of FMN cofactor were found to induce conformational changes in the FMN domain. Herein, molecular dynamics (MD) simulation is used to gain insight into the latter phenomenon at the atomistic level.

Understanding the interaction of block copolymers with DMPC lipid bilayer using coarse-grained molecular dynamics simulations.

In this paper, we present a computational model of the adsorption and percolation mechanism of poloxamers (poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO) triblock copolymers) across a 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) lipid bilayer. A coarse-grained model was used to cope with the long time scale of the percolation process. The simulations have provided details of the interaction mechanism of Pluronics with lipid bilayer.

The role of active-site Phe87 in modulating the organic co-solvent tolerance of cytochrome P450 BM3 monooxygenase.

Understanding the effects of organic co-solvents on protein structure and function is pivotal to engineering enzymes for biotransformation in non-aqueous solvents. The effects of DMSO on the catalytic activity of cytochrome P450 BM3 have previously been investigated and the importance of Phe87 in its organic co-solvent tolerance was identified. To probe the DMSO inactivation mechanism and the functional role of Phe87 in modulating the organic co-solvent tolerance of P450 BM3, the haem domain (Thr1-Leu455) of the F87A variant was cocrystallized in the presence of 14%(v/v) and 28%(v/v) DMSO.

Structure and dynamics of dodecaborate clusters in water.

We have studied using molecular dynamics simulations the interaction of the dodecaborate anion, B(12)H(12)(2-), and its amino, trimethyl, and triethyl derivatives with water molecules. We found peculiar organization of the water molecules in the first solvation shell with the formation of a dihydrogen bond between the hydrogen atoms of the anions and the hydrogen atoms of the water molecules. The simulations also show that the organization of the hydration shell is strongly influenced by the substituents in the anions.