Comparison of predicted native structures of Met-enkephalin based on various accessible-surface-area solvent models.

We examine the variation and similarity of the native structures predicted from various accessible-surface-area solvent models for peptide Met-enkephalin. Both ECEPP/2 and ECEPP/3 force fields have been used in conjunction with ten different sets of accessible-surface-area parameterization. The native structures were determined by an implementation of the basin hopping Monte Carlo technique. The results suggest that the implicit solvent models examined in this study should be employed in computer simulations with extreme caution. In addition, the effect of fixing or not fixing the peptide angles omega has been examined. We conclude that fixing omega generally gives rise to a poor prediction.

Modeling the separation of macromolecules: a review of current computer simulation methods.

Theory and numerical simulations play a major role in the development of improved and novel separation methods. In some cases, computer simulations predict counterintuitive effects that must be taken into account in order to properly optimize a device. In other cases, simulations allow the scientist to focus on a subset of important system parameters. Occasionally, simulations even generate entirely new separation ideas! In this article, we review the main simulation methods that are currently being used to model separation techniques of interest to the readers of Electrophoresis. In the first part of the article, we provide a brief description of the numerical models themselves, starting with molecular methods and then moving towards more efficient coarse-grained approaches. In the second part, we briefly examine nine separation problems and some of the methods used to model them. We conclude with a short discussion of some notoriously hard-to-model separation problems and a description of some of the available simulation software packages.

Computational study of the Trp-cage miniprotein based on the ECEPP/3 force field.

Using a newly developed Monte Carlo global optimization method called basin paving, we have performed an ab initio computation for the structure of Trp-cage based on the ECEPP/3 force field in vacuo. The lowest energy minimum has been located. Its corresponding configuration is comparable to the native structure of Trp-cage (PDB code 1L2Y) with a backbone root mean square deviation of 2.24 A.

Monte Carlo basin paving: an improved global optimization method.

We propose a global optimization procedure, basin paving, which is based on the combination of the optimization strategies behind basin hopping and energy landscape paving. As an example, we describe its application in the protein structure prediction by examining two well-studied peptides, where we have found lower potential energy minima than previously located. We also compare the statistics of the searching trajectories produced by basin paving, basin hopping, and energy landscape paving.

Activation kinetics of zipper molecular beacons.

Proteases play key roles in the regulation of normal cellular function, and thus, their deregulation leads to many disease states. Molecular beacons are promising protease-imaging probes for the detection and characterization of disease as well as for the evaluation of treatment. Inspired by this, we examined the efficiency of zipper molecular beacons (ZMBs) as imaging probes. First, we showed experimentally that the symmetrical ZMB (zip5e5r), bearing 5-arginine and 5-glutamate arms, is as efficient as the asymmetrical zip5e8r in enhancing cell uptake but without the dark toxicity exhibited by the asymmetric zipper. Also, zip5e5r was shown to dissociate more efficiently at pH's greater than 5. Using a simple two-state binding model, we attributed this to a larger number of charge-pair conformations for zip5e8r. We then measured the ability of soluble matrix metalloproteinases (MMPs) to cleave zip5e5r, and compared their cleavage efficiency with the original photodynamic molecular beacon (PMB). Finally, as a first step toward understanding our observations quantitatively, we simulated the native structures of the peptides GPLGLARK and EGPLGLARRK with charged termini NH3(+) and COO(-) that approximate the PMB and ZMB (with one pair of arginine/glutamate electrostatic zipper), respectively. We concluded that inclusion of the zipper changes the native structure of the MBs, altering the cleavage efficiency of different MMPs.

Beam coordinate transformations from DICOM to DOSXYZnrc.

Digital imaging and communications in medicine (DICOM) format is the de facto standard for communications between therapeutic and diagnostic modalities. A plan generated by a treatment planning system (TPS) is often exported in DICOM format. BEAMnrc/DOSXYZnrc is a widely used Monte Carlo (MC) package for modelling the Linac head and simulating dose delivery in radiotherapy. It has its own definition of beam orientation, which is not in compliance with the one defined in the DICOM standard. MC dose calculations using information from TPS generated plans require transformation of beam orientations to the DOSXYZnrc coordinate system (c.s.) and the transformation is non-trivial. There have been two studies on the coordinate transformations. The transformation equation sets derived have been helpful to BEAMnrc/DOSXYZnrc users. However, the transformation equation sets are complex mathematically and not easy to program. In this study, we derive a new set of transformation equations, which are more compact, easily understandable, and easier for computational implementation. The derivation of the polar angle θ and the azimuthal angle φ used by DOSXYZnrc is similar to the existing studies by applying a series of rotations to a vector in DICOM patient c.s. The derivation of the beam rotation ϕ(col) for DOSXYZnrc, however, is different. It is obtained by a direct combination of the actual collimator rotation with the projection of the couch rotation to the collimator rotating plane. Verification of the transformation has been performed using clinical plans. The comparisons between TPS and MC results show very good geometrical agreement for field placements, together with good agreement in dose distributions.

Determination of structural transitions of atomic clusters from local and global bond orientational order parameters.

Designing an effective order parameter for the identification of geometries in atomic clusters is an important step toward understanding the structural transitions occurring in these systems. We propose a method that simultaneously utilizes the local and global bond orientational order parameters for structural transitions. When applied to Lennard-Jones clusters at finite temperature over the size range 30< or =N< or =146, this method identified all the major geometries: icosahedra with Mackay overlayers, icosahedra with anti-Mackay overlayers, decahedra, octahedra, and tetrahedra. From the distributions of these geometries as a function of temperatures on clusters containing 38, 75, and 98 atoms, we are able to interpret all transition types without ambiguity.

Conformational study of Met-enkephalin based on the ECEPP force fields.

We report a computational study of the small peptide Met-enkephalin based on the ECEPP/2 and ECEPP/3 force fields using the basin paving method. We have located a new global minimum when using the ECEPP/3 force field with peptide angles omega fixed at 180 degrees. With this new result, we can conclude that the lowest energy configurations of Met-enkephalin predicted based on all four versions of ECEPP have a classic gamma-turn centered at residue Gly3 and a beta-turn at residues Gly3-Phe4. However, minor differences between the structures also exist.

Asynchronous multicanonical basin hopping method and its application to cobalt nanoclusters.

The multicanonical basin hopping (MUBH) method, which uses a multicanonical weight in the basin hopping (BH) Monte Carlo method, was found to be very efficient for global optimization of large-scale systems such as Lennard-Jones clusters containing more than 150 atoms. We have implemented an asynchronous parallel version of the MUBH method using the message passing interface (MPI) to take advantage of the full usage of multiprocessors in either a homogeneous or heterogeneous computational environment. Based on the intrinsic properties of the Monte Carlo method, this MPI implementation used the task parallelism to minimize interthread data communication. For a Co nanocluster consisting of N atoms, we have applied the asynchronous multicanonical basin hopping (AMUBH) method (for 181 < N < or = 200), together with BH (for 2 < or = N < 150) and MUBH (for 150 < or = N < or = 180), to search for the molecular configuration of the global energy minimum. AMUBH becomes the only practical computational scheme for locating the energy minimum within realistic computational time for a relatively large cluster.

Multicanonical basin hopping: a new global optimization method for complex systems.

We introduce a new optimization algorithm that combines the basin-hopping method, which can be used to efficiently map out an energy landscape associated with minima, with the multicanonical Monte Carlo method, which encourages the system to move out of energy traps during the computation. As an example of implementing the algorithm for the global minimization of a multivariable system, we consider the Lennard-Jones systems containing 150-185 particles, and find that the new algorithm is more efficient than the original basin-hopping method.