Brownian dynamics of a compressed polymer brush model. Off-equilibrium response as a function of surface coverage and compression rate.

We study the compressive behaviour of a polymer-covered surface (i.e., a "polymer brush") using Brownian dynamics simulations.

Off-equilibrium response of grafted polymer chains subject to a variable rate of compression.

We present Brownian dynamics simulations of single grafted semiflexible chains (i.e., "polymer mushrooms") with varying persistence lengths, intra-chain interactions, and subject to confinement.

Simulated force-induced unfolding of alpha-helices: dependence of stretching stability on primary sequence.

Some of the principles that determine a protein's native fold can be probed with techniques for single-molecule manipulation. Yet, understanding the effects of an external force at atomic level still requires computer simulations. Here, we employ a novel protocol for steered molecular dynamics that allows for internal energy redistribution (and possibly, re-equilibration) while the molecule is subject to a mechanical perturbation.

Path-space ratio as a molecular shape descriptor of polymer conformation.

Polymers at interfaces exhibit properties that cannot be completely captured by descriptors of mean molecular size. Recent work in the literature shows that a combined analysis of mean size and chain entanglement provides a more discriminating approach to understanding the onset of configurational transitions in these systems. Usually, chain entanglement is characterized by properties such as the mean overcrossing number or the chain's writhe; these are powerful properties but their evaluation can be computationally demanding.

A measure of folding complexity for d-dimensional polymers.

A measure of folding characterizes aspects of the instantaneous organization of a polymer chain in space. For three-dimensional polymers (D = 3), one such measure is the mean overcrossing number. An intuitively similar property, the radial intersection number, has been proposed as a tool to characterize "folding features" in two-dimensional polymers (D = 2).

Geometrical modelling of Ohmic conductance in ion channels.

In an Ohmic model, channel conductivity can be described in terms of the geometry of a conducting cable. The essential features of such devices are the arc length of the curve describing the channel's longitudinal path, and the cross-sectional areas transversal to this curve. In a first approximation, conducting channels can be represented by an average molecular shape with estimated lengths and cross-sectional areas.

Proteins in vacuo: denaturing and folding mechanisms studied with computer-simulated molecular dynamics.

Mounting evidence from experiments suggests that the native fold in solution is metastable in dehydrated proteins. Results from a number of experiments that use mass spectrometry indicate also that folding-unfolding transitions take place in protein ions even in the absence of water. These observations on anhydrous proteins call for a re-evaluation of our understanding of the folding transition.

Addendum to "Quantitative measure of folding in two-dimensional polymers".

Recently, we introduced a measure of folding complexity for two-dimensional polymers, N macro, the mean radial intersection number [Phys. Rev. E 59, 4209 (1999)].

Unfolded in vacuo lysozyme folds into native, quasinative, and compact structures.

We show that the relaxation dynamics of unfolded in vacuo lysozyme is not random. Analyses of molecular dynamics trajectories in a convenient space of molecular shape descriptors reveal a "favored" pattern of transitions leading to stable conformations. The relaxation paths exhibit a balanced change in shape features: globular spheroids are formed slowly enough to allow the proper entanglement of secondary-structural elements.

Analytical estimation of scaling behavior for the entanglement complexity of a bond network.

Geometrical entanglements in a polymer network can be characterized in terms of the mean number of projected bond-bond crossings, N. Here, we present an analytical method to study the dependence of N on the number of bonds in the network, n. Our approach shows the occurrence of power-law scaling, N - n(beta).

Structural transitions in neutral and charged proteins in vacuo.

In vacuo proteins provide a simple laboratory to explore the roles of sequence, temperature, charge state, and initial configuration in protein folding. Moreover, by the very absence of solvent, the study of anhydrous proteins in vacuo will also help us to understand specific environmental effects. From the experimental viewpoint, these systems are now beginning to be characterized at low resolution.

Characterization of fold diversity among proteins with the same number of amino acid residues.

Chain entanglements provide a simple and global measure of folding in a macromolecule. The complexity of these entanglements can be expressed by the pattern of projected bond-bond crossings, or "overcrossings", associated with the molecular backbone. In this work, we use this approach to characterize quantitatively the range of tertiary folds observed in proteins with a given chain length.

Electron-density-dependent fused-sphere surfaces derived from pseudopotential calculations.

Fused-sphere surfaces can be used to mimic a molecular "boundary" associated with a constant value of the electron density. The simplest of such fused-sphere models are constructed by using the atomic radii for the spherical isodensity surfaces of individual atoms. In this work, we discuss the extension of this model to molecules containing atoms beyond the second row.

Heuristic lipophilicity potential for computer-aided rational drug design.

In this contribution we suggest a heuristic molecular lipophilicity potential (HMLP), which is a structure-based technique requiring no empirical indices of atomic lipophilicity. The input data used in this approach are molecular geometries and molecular surfaces. The HMLP is a modified electrostatic potential, combined with the averaged influences from the molecular environment.

Three-dimensional lipophilicity characterization of molecular pores and channel-like cavities.

Molecular lipophilicity is a useful property for assessing molecular similarity or complementarity within the context of computer-aided drug design. As well, local contributions to solvent affinity help us to understand both dynamics and conformational stability in biomolecules. In this work, we discuss an approach to characterize the local contributions to hydrophobicity by using one- and two-dimensional representations of molecular channel-like cavities.

Modeling lipophilicity from the distribution of electrostatic potential on a molecular surface.

Molecular lipophilicity L is represented as a function of four surface electrostatic potential descriptors: L = f(B+F, B-F, B+R, B-R). Each B descriptor is computed from the products of elements of molecular surface area, delta(si), and the molecular electrostatic potential (MEP), V(ri), at the center of an area element: B = sigma(i) delta(si) V(r(i)). Octanol-water partition coefficients (P(ow)) are correlated with these four surface-MEP descriptors: log P(ow) = c0 + c1B+F + c2B-F + c3B+R + c4B-R.

Interrelation between electrostatic and lipophilicity potentials on molecular surfaces.

Molecular electrostatics and lipophilicity are two important properties included in quantitative structure-activity relationships (QSARs) employed for rational drug design. The molecular electrostatic potential (MEP) provides information on the position, distribution, and extent of electrophilic and nucleophilic regions around a molecule. Similarly, the solvent affinity can be represented by a local phenomenological potential of semiempirical nature: the molecular lipophilicity potential (MLP).

Overcrossing spectra of protein backbones: characterization of three-dimensional molecular shape and global structural homologies.

A procedure is developed and applied to characterize the global shape and folding features of the backbone of a chain molecule. The methodology is based on the following concept: the probability of observing a rigid placement of a backbone in 3-space as a projected curve with N overcrossings. The numerical computation of these probabilities allows one to construct the overcrossing spectrum of a macromolecule at a given configuration.

Global characterization of protein secondary structures. Analysis of computer-modeled protein unfolding.

Analyses of structural and molecular shape changes undergone by a protein during an unfolding process are presented. The procedure, based on a spherical shape map method, provides a topological description of a three-dimensional macromolecular structure. Local properties of the backbone are used to derive a global characterization of its fold.

Implementing knot-theoretical characterization methods to analyze the backbone structure of proteins: application to CTF L7/L12 and carboxypeptidase A inhibitor proteins.

In this work we apply a recently developed method for characterizing the shape of the tertiary structure of proteins. The approach is based on a combination of graph- and knot-theoretical characterizations of Cartesian projections of the space curve describing the protein backbone. The proposed technique reduces the essential shape features to a topologically based code formed by a sequence of knot symbols and polynomials.

A method for the characterization of foldings in protein ribbon models.

The ribbon model of chain macromolecules is a useful tool for analyzing some of the large-scale shape features of these complex systems. Up to now, the ribbon model has been used mostly to produce graphical displays, which are usually analyzed by visual inspection. In this work we suggest a computational method for characterizing automatically, in a concise and algebraic fashion, some of the important shape features of these ribbon models.