Biomedical subjects

Eldon G Emberly

Publications and source records attributed to Eldon G Emberly.

6 recordsLinked to original sources

PubMed2004

Flexibility of beta-sheets: principal component analysis of database protein structures.

Protein folds are built primarily from the packing together of two types of structures: alpha-helices and beta-sheets. Neither structure is rigid, and the flexibility of helices and sheets is often important in determining the final fold (e.g., coiled coils and beta-barrels). Recent work has quantified the flexibility of alpha-helices using a principal component analysis (PCA) of database helical structures (J. Mol. Bio. 2003, 327, pp. 229-237). Here, we extend the analysis to beta-sheet flexibility using PCA on a database of beta-sheet structures. For sheets of varying dimension and geometry, we find two dominant modes of flexibility: twist and bend. The distributions of amplitudes for these modes are found to be Gaussian and independent, suggesting that the PCA twist and bend modes can be identified as the soft elastic normal modes of sheets. We consider the scaling of mode eigenvalues with sheet size and find that parallel beta-sheets are more rigid than antiparallel sheets over the entire range studied. Finally, we discuss the application of our PCA results to modeling and design of beta-sheet proteins.

Databases, Protein↗

PubMed2003

The smallest molecular switch.

Ab initio total energy calculations reveal benzene-dithiolate molecules on a gold surface, contacted by a monatomic gold STM tip to have two classes of low-energy conformations with differing symmetries. Lateral motion of the tip or excitation of the molecule cause it to change from one conformation class to the other and to switch between a strongly and a weakly conducting state. Thus, surprisingly, despite their apparent simplicity, these Au/BDT/Au nanowires are shown to be electrically bistable switches, the smallest two-terminal molecular switches to date.

Journal Article↗

PubMed2003

Flexibility of alpha-helices: results of a statistical analysis of database protein structures.

Alpha-helices stand out as common and relatively invariant secondary structural elements of proteins. However, alpha-helices are not rigid bodies and their deformations can be significant in protein function (e.g. coiled coils). To quantify the flexibility of alpha-helices we have performed a structural principal-component analysis of helices of different lengths from a representative set of protein folds in the Protein Data Bank. We find three dominant modes of flexibility: two degenerate bend modes and one twist mode. The data are consistent with independent Gaussian distributions for each mode. The mode eigenvalues, which measure flexibility, follow simple scaling forms as a function of helix length. The dominant bend and twist modes and their harmonics are reproduced by a simple spring model, which incorporates hydrogen-bonding and excluded volume. As an application, we examine the amount of bend and twist in helices making up all coiled-coil proteins in SCOP. Incorporation of alpha-helix flexibility into structure refinement and design is discussed.

Databases, Protein↗

PubMed2002

Designability of alpha-helical proteins.

A typical protein structure is a compact packing of connected alpha-helices and/or beta-strands. We have developed a method for generating the ensemble of compact structures a given set of helices and strands can form. The method is tested on structures composed of four alpha-helices connected by short turns. All such natural four-helix bundles that are connected by short turns seen in nature are reproduced to closer than 3.6 A per residue within the ensemble. Because structures with no natural counterpart may be targets for ab initio structure design, the designability of each structure in the ensemble-defined as the number of sequences with that structure as their lowest-energy state-is evaluated using a hydrophobic energy. For the case of four alpha-helices, a small set of highly designable structures emerges, most of which have an analog among the known four-helix fold families; however, several packings and topologies with no analogs in protein database are identified.

Amino Acid Sequence↗

PubMed2002

Identifying proteins of high designability via surface-exposure patterns.

Using an off-lattice model, we fully enumerate folded conformations of polypeptide chains of up to N = 19 monomers. Structures are found to differ markedly in designability, defined as the number of sequences with that structure as a unique lowest-energy conformation. We find that designability is closely correlated with the pattern of surface exposure of the folded structure. For longer chains, complete enumeration of structures is impractical. Instead, structures can be randomly sampled, and relative designability estimated either from designability within the random sample, or directly from surface-exposure pattern. We compare the surface-exposure patterns of those structures identified as highly designable to the patterns of naturally occurring proteins.

Hydrophobic and Hydrophilic Interactions↗

PubMed2002

Charging effects, forces, and conduction in molecular wire systems.

Recently, experiments have shown that effects arising from charging and conformational changes in a molecular wire due to an applied voltage bias can have a significant influence on the transport characteristics of the system. We introduce a tractable theoretical approach based on Landauer theory and total energy methods that treats transport nonlinearities, conformational changes, and charging effects in molecular wires in a unified way. We apply this approach to molecular wires consisting of short chain molecules with different electronic and structural properties bonded to metal contacts. We find that the nonlinear conductance characteristics of these systems are remarkably similar and can be understood in terms of a single physical mechanism. We predict that negative differential resistance should occur at high bias in such molecular wires due to the combined effects of charging and conformational changes on their electronic structure.

Electric Conductivity↗