GA-guided mD-VcMD: A genetic-algorithm-guided method for multi-dimensional virtual-system coupled molecular dynamics.

We introduced a conformational sampling method in an earlier report: The multi-dimensional virtual-system coupled molecular dynamics (mD-VcMD) enhances conformational sampling of a biomolecular system by computer simulations. Herein, new sampling method, a subzone-based mD-VcMD, is presented as an extension of mD-VcMD. Then, the subzone-based method is extended further using a genetic algorithm (GA) named the GA-guided mD-VcMD.

Molecular Interaction Mechanism of a 14-3-3 Protein with a Phosphorylated Peptide Elucidated by Enhanced Conformational Sampling.

Enhanced conformational sampling, a genetic-algorithm-guided multidimensional virtual-system coupled molecular dynamics, can provide equilibrated conformational distributions of a receptor protein and a flexible ligand at room temperature. The distributions provide not only the most stable but also semistable complex structures and propose a ligand-receptor binding process. This method was applied to a system consisting of a receptor protein, 14-3-3ε, and a flexible peptide, phosphorylated myeloid leukemia factor 1 (pMLF1).

Hydrogen bond donors and acceptors are generally depolarized in α-helices as revealed by a molecular tailoring approach.

Hydrogen-bond (H-bond) interaction energies in α-helices of short alanine peptides were systematically examined by precise density functional theory calculations, followed by a molecular tailoring approach. The contribution of each H-bond interaction in α-helices was estimated in detail from the entire conformation energies, and the results were compared with those in the minimal H-bond models, in which only H-bond donors and acceptors exist with the capping methyl groups. The former interaction energies were always significantly weaker than the latter energies, when the same geometries of the H-bond donors and acceptors were applied.

Density functional study of molecular interactions in secondary structures of proteins.

Proteins play diverse and vital roles in biology, which are dominated by their three-dimensional structures. The three-dimensional structure of a protein determines its functions and chemical properties. Protein secondary structures, including α-helices and β-sheets, are key components of the protein architecture.

Impaired tight junctions obstruct stratum corneum formation by altering polar lipid and profilaggrin processing.

Background: The stratum corneum (SC) is a well-known structure responsible for the cutaneous barrier. Tight junctions (TJs) function as a paracellular barrier beneath the SC and are involved in the cutaneous barrier. It remains unclear how TJs are involved in the cutaneous barrier.

Changes in epidermal hyaluronan metabolism following UVB irradiation.

Background: Hyaluronan (HA) plays a role in keratinocyte proliferation and differentiation, and have shown different biological activities depending on its molecular mass. While many studies have shown changes in the amount of HA after UVB irradiation, molecular mass change remains to be elucidated.

Objective: To investigate the change in the molecular mass of HA after UVB irradiation in mouse epidermis.

Characterization of tight junctions and their disruption by UVB in human epidermis and cultured keratinocytes.

It has not been confirmed whether tight junctions (TJs) function as a paracellular permeability barrier in adult human skin. To clarify this issue, we performed a TJ permeability assay using human skin obtained from abdominal plastic surgery. Occludin, a marker protein of TJs, was expressed in the granular layer, in which a subcutaneously injected paracellular tracer, Sulfo-NHS-LC-Biotin (556.

Ultrasonic tissue characterization of photodamaged skin by scanning acoustic microscopy.

The aim of this study was to ultrasonically characterize photodamaged skin of the elderly at the microscopic level using scanning acoustic microscopy which showed two-dimentional distribution of sound speed in the skin section. We confirmed that the expression level of the elastin gene was increased in the preauricular skin (photodamaged area), compared with postauricular skin (photo-protected area). The expression level of the procollagen gene was also increased in the preauricular skin compared with postauricular skin.

Characteristics of the epidermis and stratum corneum of hairless mice with experimentally induced diabetes mellitus.

Diabetes mellitus induces many pathophysiologic changes in the skin. Even so, dermatologists still lack an animal model of diabetes that enables the direct evaluation of the various functional properties of the skin. Our group induced two types of an experimental type 1 diabetes model in hairless mice by administering either streptozotocin or alloxan, in order to examine the properties of the stratum corneum and epidermis of these animals.