Erythematous Plaques and Tense Bullae in an Infant.

Although often thought of as a disease of the elderly, bullous pemphigoid is the second most common bullous disease in infants. Infantile bullous pemphigoid is extremely rare and may be easily confused with other skin diseases such as epidermolysis bullosa and chronic bullous disease of childhood. There appears to be a paucity of literature on unique clinical presentations of infantile bullous pemphigoid.

Changes in Disease Activity and Damage Over Time in Patients With Morphea.

Importance: Prospective studies of the disease course in patients with morphea are lacking, particularly those comparing adults and children.

Objective: To investigate the disease course in patients with morphea treated with standard-of-care therapy using validated clinical outcome measures.

Design, Setting, And Participants: Prospective cohort study of 130 adults and children from the Morphea in Adults and Children cohort with at least 2 years of clinical follow-up and Localized Scleroderma Cutaneous Assessment Tool scores recorded at each study visit.

Serial tempering without exchange.

Serial tempering is a computational method that turns the temperature T (or more generally any independent λ parameter) into a dynamical variable. It is shown that, under conditions for which this variable is fast, serial tempering is equivalent to the umbrella sampling method with a single effective potential. This equivalence is demonstrated using both a small one-dimensional system and a small solvated peptide.

Energy landscape of the trpzip2 peptide.

Replica exchange simulations are used to study the energy landscape of trpzip2, a model beta-hairpin system, using the AMBER99sb force field and explicit solvent. The total simulation time is 300 ns per replica (approximately 10 mus total). The trp side chains are observed to adopt multiple packing arrangements with a freezing temperature below 273 K in the simulated system.

Test of the Gouy-Chapman theory for a charged lipid membrane against explicit-solvent molecular dynamics simulations.

A wealth of experimental data has verified the applicability of the Gouy-Chapman (GC) theory to charged lipid membranes. Surprisingly, a validation of GC by molecular dynamics (MD) simulations has been elusive. Here, we report a test of GC against extensive MD simulations of an anionic lipid bilayer solvated by water at different concentrations of NaCl or KCl.

How Efficient Is Replica Exchange Molecular Dynamics? An Analytic Approach.

Replica exchange molecular dynamics (REMD) has become a standard technique for accelerating relaxation in biosimulations. Despite its widespread use, questions remain about its efficiency compared with conventional, constant temperature molecular dynamics (MD). An analytic approach is taken to describe the relative efficiency of REMD with respect to MD.

A method to determine dielectric constants in nonhomogeneous systems: application to biological membranes.

Continuum electrostatic models have had quantitative success in describing electrostatic-mediated phenomena on atomistic scales; however, there continues to be significant disagreement about how to assign dielectric constants in mixed, nonhomogeneous systems. We introduce a method for determining a position-dependent dielectric profile from molecular dynamics simulations. In this method, the free energy of introducing a test charge is computed two ways: from a free energy perturbation calculation and from a numerical solution to Poisson's Equation.

Determining the solution conformational entropy of O-linked oligosaccharides at quasi-physiological conditions: size-exclusion chromatography and molecular dynamics.

The physiological functions of oligosaccharides are influenced by a number of structural parameters such as anomeric configuration, glycosidic linkage, and degree of polymerization. These parameters affect the conformation of the oligosaccharides which, in turn, is responsible for characteristics such as aptameric and enzymatic binding, chiral recognition, and the structural targeting of bacterial and parasitic recognition events. Here, we measure the solution conformational entropy (DeltaS) of two series of oligosaccharides, linear malto- and cellooligosaccharides, using size-exclusion chromatography (SEC).

Quantitative computer simulations of biomolecules: a snapshot.

A recent workshop titled "Quantitative Computational Biophysics" at Florida State University provided an overview of the state of the art in quantitative modeling of biomolecular systems. The presentations covered a wide range of interrelated topics, including the development and validation of force fields, the modeling of protein-protein interactions, the sampling of conformational space, and the assessment of equilibration and statistical errors. Substantial progress in all these areas was reported.

Replica exchange simulation of reversible folding/unfolding of the Trp-cage miniprotein in explicit solvent: on the structure and possible role of internal water.

We simulate the folding/unfolding equilibrium of the 20-residue miniprotein Trp-cage. We use replica exchange molecular dynamics simulations of the AMBER94 atomic detail model of the protein explicitly solvated by water, starting from a completely unfolded configuration. We employ a total of 40 replicas, covering the temperature range between 280 and 538 K.

Indole localization in lipid membranes revealed by molecular simulation.

It is commonly known that the amino acid residue tryptophan and its side-chain analogs, e.g., indole, are strongly attracted to the interfacial region of lipid bilayers.

Folding is not required for bilayer insertion: replica exchange simulations of an alpha-helical peptide with an explicit lipid bilayer.

We implement the replica exchange molecular dynamics algorithm to study the interactions of a model peptide (WALP-16) with an explicitly represented DPPC membrane bilayer. We observe the spontaneous, unbiased insertion of WALP-16 into the DPPC bilayer and its folding into an alpha-helix with a transbilayer orientation. The free energy surface suggests that the insertion of the peptide into the DPPC bilayer precedes secondary structure formation.

Simulation of the folding equilibrium of alpha-helical peptides: a comparison of the generalized Born approximation with explicit solvent.

We compare simulations using the generalized Born/surface area (GB/SA) implicit solvent model with simulations using explicit solvent (transferable intermolecular potential 3 point, TIP3P) to test the GB/SA algorithm. We use the replica exchange molecular dynamics method to sample the conformational phase space of two alpha-helical peptides, A21 and the Fs, by using two different classical potentials and both water models. We find that when using GB/SA: (i) A21 is predicted to be more helical than the Fs peptide at all temperatures; (ii) the native structure of the Fs peptide is predicted to be a helical bundle instead of a single helix; and (iii) the persistence length and most probable end-to-end distance are too large in the unfolded state when compared against the explicit solvent simulations.

Peptide folding simulations.

Developments in the design of small peptides that mimic proteins in complexity, recent advances in nanosecond time-resolved spectroscopy methods to study peptides and the development of modern, highly parallel simulation algorithms have come together to give us a detailed picture of peptide folding dynamics. Two newly implemented simulation techniques, parallel replica dynamics and replica exchange molecular dynamics, can now describe directly from simulations the kinetics and thermodynamics of peptide formation, respectively. Given these developments, the simulation community now has the tools to verify and validate simulation protocols and models (forcefields).

Specific and nonspecific collapse in protein folding funnels.

Experiments with fast folding proteins are beginning to address the relationship between collapse and folding. We investigate how different scenarios for folding can arise depending on whether the folding and collapse transitions are concurrent or whether a nonspecific collapse precedes folding. Many earlier studies have focused on the limit in which collapse is fast compared to the folding time; in this work we focus on the opposite limit where, at the folding temperature, collapse and folding occur simultaneously.