Reverse Mapping of Coarse Grained Polyglutamine Conformations from PRIME20 Sampling.

An inverse coarse-graining protocol is presented for generating and validating atomistic structures of large (bio-) molecules from conformations obtained via a coarse-grained sampling method. Specifically, the protocol is implemented and tested based on the (coarse-grained) PRIME20 protein model (P20/SAMC), and the resulting all-atom conformations are simulated using conventional biomolecular force fields. The phase space sampling at the coarse-grained level is performed with a stochastical approximation Monte Carlo approach.

"Organized stress" for robust scale-up of intensified production process with fed-batch seed bioreactor.

Process intensification has been widely used for many years in the mammalian biomanufacturing industry to increase productivity, agility and flexibility while reducing production costs. The most commonly used intensified processes are operated using a perfusion or fed-batch seed bioreactor enabling a higher than usual seeding density in the fed-batch production bioreactor. Hence, as part of the growth phase is shifted to the seed bioreactor, there is a lower split ratio, which increases the criticality of the seed bioreactor and could impact production performance.

Aggregation and crystallization of small alkanes.

We present a computer simulation study of the aggregation and ordering of short alkane chains using a united atom model description. Our simulation approach allows us to determine the density of states of our systems and, from those, their thermodynamics for all temperatures. All systems show a first order aggregation transition followed by a low-temperature ordering transition.

Thermodynamics and Conformations of Single Polyalanine, Polyserine, and Polyglutamine Chains within the PRIME20 Model.

Understanding the conformational behavior of proteins has been a long-standing challenge to which computer simulations could contribute significantly. This concerns the folding behavior of proteins as well as the conformational statistics of intrinsically disordered proteins. A well-converged sampling of the conformational statistics over a broad range of control parameters is computationally extremely challenging and best addressed by coarse-grained modeling, for example, with an intermediate resolution model like the PRIME20 model.

Collective dynamics of pedestrians in a corridor: An approach combining social force and Vicsek models.

We study the pedestrian motion along a corridor in a nonpanic regime, as usually happens in evacuation scenarios in, e.g., schools, hospitals, or airports, by means of Monte Carlo simulations.

Morphology and thermodynamics of polymers with monofunctional hydrogen bonding ends in dilute and semidilute concentration.

Rheological properties of supramolecular polymers (SMPs) depend on their equilibrium structure including the size, the number, and the topology of aggregates. A polymer with a hydrogen bonding (H-bonding) motif at both ends is one widely used precursor to build SMPs. Due to the complex interplay between chain stiffness, H-bonding interaction, polarity along a chain, and polymer conformational entropy, it is difficult to theoretically predict the structure of SMPs.

Diagrams of States of Single Flexible-Semiflexible Multi-Block Copolymer Chains: A Flat-Histogram Monte Carlo Study.

The combination of flexibility and semiflexibility in a single molecule is a powerful design principle both in nature and in materials science. We present results on the conformational behavior of a single multiblock-copolymer chain, consisting of equal amounts of Flexible (F) and Semiflexible (S) blocks with different affinity to an implicit solvent. We consider a manifold of macrostates defined by two terms in the total energy: intermonomer interaction energy and stiffness energy.

The Conformational Ensemble of Polyglutamine-14 Chains: Specific Influences of Solubility Tail and Chromophores.

We address polyglutamine-14 in aqueous solution with specific chromophores and a solubility chain by means of a multiscale simulation approach, combining atomistic molecular dynamics simulations and coarse-grained Monte-Carlo conformational sampling. Despite the intrinsically disordered nature of the amyloidogenic polyglutamine, we observe transient characteristic structural motifs which exhibit a specific hydrogen bonding pattern. We illustrate the relationship between structure pattern and the distance distribution of a pair of chromophores attached to the peptide termini, in light of specific influence of a short solubility tail and the chromophores themselves on the conformational ensemble.

Thermodynamics of single polyethylene and polybutylene glycols with hydrogen-bonding ends: A transition from looped to open conformations.

A variety of linear polymer precursors with hydrogen bonding motifs at both ends enable us to design supramolecular polymer systems with tailored macroscopic properties including self-healing. In this study, we investigate thermodynamic properties of single polyethylene and polybutylene glycols with hydrogen bonding motifs. In this context, we first build a coarse-grained model of building blocks of the supramolecular polymer system based on all-atom molecular structures.

Chain relaxation in thin polymer films: turning a dielectric type-B polymer into a type-A' one.

A molecular dynamics simulation study of chain relaxation in a thin polymer film is presented, studying the dielectric response of a random copolymer of cis and trans 1,4-polybutadiene, a type B polymer without net chain dipole moment, confined between graphite walls. We stress the orientational effect of the attractive walls, inducing polarization in the vicinity of the walls, while the center of the film stays bulk-like. This polarization leads to a net dipole moment of the adsorbed chains, which is perpendicular to their end-to-end vector, which we termed as type A' behavior.

On the Pseudo Phase Diagram of Single Semi-Flexible Polymer Chains: A Flat-Histogram Monte Carlo Study.

Local stiffness of polymer chains is instrumental in all structure formation processes of polymers, from crystallization of synthetic polymers to protein folding and DNA compactification. We present Stochastic Approximation Monte Carlo simulations-a type of flat-histogram Monte Carlo method-determining the density of states of a model class of single semi-flexible polymer chains, and, from this, their complete thermodynamic behavior. The chains possess a rich pseudo phase diagram as a function of stiffness and temperature, displaying non-trivial ground-state morphologies.

On the polymer physics origins of protein folding thermodynamics.

A remarkable feature of the spontaneous folding of many small proteins is the striking similarity in the thermodynamics of the folding process. This process is characterized by simple two-state thermodynamics with large and compensating changes in entropy and enthalpy and a funnel-like free energy landscape with a free-energy barrier that varies linearly with temperature. One might attribute the commonality of this two-state folding behavior to features particular to these proteins (e.

Multidimensional stochastic approximation Monte Carlo.

Stochastic Approximation Monte Carlo (SAMC) has been established as a mathematically founded powerful flat-histogram Monte Carlo method, used to determine the density of states, g(E), of a model system. We show here how it can be generalized for the determination of multidimensional probability distributions (or equivalently densities of states) of macroscopic or mesoscopic variables defined on the space of microstates of a statistical mechanical system. This establishes this method as a systematic way for coarse graining a model system, or, in other words, for performing a renormalization group step on a model.

Diagram of states and morphologies of flexible-semiflexible copolymer chains: A Monte Carlo simulation.

A single copolymer chain consisting of multiple flexible (F) and semiflexible (S) blocks has been studied using a continuum bead-spring model by Stochastic Approximation Monte Carlo simulations, which determine the density of states of the model. The only difference between F and S blocks is the intramolecular bending potential, all non-bonded interactions are equal. The state diagrams for this class of models display multiple nematic phases in the collapsed state, characterized through a demixing of the blocks of different stiffness and orientational ordering of the stiff blocks.

A hybrid approach identifies metabolic signatures of high-producers for chinese hamster ovary clone selection and process optimization.

In-depth characterization of high-producer cell lines and bioprocesses is vital to ensure robust and consistent production of recombinant therapeutic proteins in high quantity and quality for clinical applications. This requires applying appropriate methods during bioprocess development to enable meaningful characterization of CHO clones and processes. Here, we present a novel hybrid approach for supporting comprehensive characterization of metabolic clone performance.

Wang-Landau simulation of Gō model molecules.

Gō-like models are one of the oldest protein modeling concepts in computational physics and have proven their value over and over for forty years. The essence of a Gō model is to define a native contact matrix for a well-defined low-energy polymer configuration, e.g.

Thermodynamics and structure of macromolecules from flat-histogram Monte Carlo simulations.

Over the last decade flat-histogram Monte Carlo simulations, especially multi-canonical and Wang-Landau simulations, have emerged as a strong tool to study the statistical mechanics of polymer chains. These investigations have focused on coarse-grained models of polymers on the lattice and in the continuum. Phase diagrams of chains in bulk as well as chains attached to surfaces were studied, for homopolymers as well as for protein-like models.

Partition function zeros and phase transitions for a square-well polymer chain.

The zeros of the canonical partition functions for flexible square-well polymer chains have been approximately computed for chains up to length 256 for a range of square-well diameters. We have previously shown that such chain molecules can undergo a coil-globule and globule-crystal transition as well as a direct coil-crystal transition. Here we show that each of these transitions has a well-defined signature in the complex-plane map of the partition function zeros.

Scattering function of semiflexible polymer chains under good solvent conditions.

Using the pruned-enriched Rosenbluth Monte Carlo algorithm, the scattering functions of semiflexible macromolecules in dilute solution under good solvent conditions are estimated both in d = 2 and d = 3 dimensions, considering also the effect of stretching forces. Using self-avoiding walks of up to N = 25,600 steps on the square and simple cubic lattices, variable chain stiffness is modeled by introducing an energy penalty ε(b) for chain bending; varying q(b) = exp (-ε(b)∕k(B)T) from q(b) = 1 (completely flexible chains) to q(b) = 0.005, the persistence length can be varied over two orders of magnitude.

Computer simulation of bottle-brush polymers with flexible backbone: good solvent versus theta solvent conditions.

By molecular dynamics simulation of a coarse-grained bead-spring-type model for a cylindrical molecular brush with a backbone chain of N(b) effective monomers to which with grafting density σ side chains with N effective monomers are tethered, several characteristic length scales are studied for variable solvent quality. Side chain lengths are in the range 5 ≤ N ≤ 40, backbone chain lengths are in the range 50 ≤ N(b) ≤ 200, and we perform a comparison to results for the bond fluctuation model on the simple cubic lattice (for which much longer chains are accessible, N(b) ≤ 1027, and which corresponds to an athermal, very good, solvent). We obtain linear dimensions of the side chains and the backbone chain and discuss their N-dependence in terms of power laws and the associated effective exponents.

Structure of bottle brush polymers on surfaces: weak versus strong adsorption.

Large-scale Monte Carlo simulations are presented for a coarse-grained model of cylindrical molecular brushes adsorbed on a flat structureless substrate, varying both the chain length N of the side chains and the backbone chain length N(b). For the case of good solvent conditions, both the cases of weak adsorption (only 10 to 15% of the monomers being bound to the surface) and strong adsorption (~40% of the monomers being bound to the surface, forcing the bottle brush into an almost 2D conformation) are studied. We focus on the scaling of the total linear dimensions of the cylindrical brush with both chain lengths N and N(b), demonstrating a crossover from rod-like behavior (for not very large N(b)) to the scaling of 2D self-avoiding walks.

Mesophase formation in two-component cylindrical bottlebrush polymers.

When two types of side chains (A,B) are densely grafted to a (stiff) backbone and the resulting bottlebrush polymer is in a solution under poor solvent conditions, an incompatibility between A and B leads to microphase separation in the resulting cylindrical brush. The possible types of ordering are reminiscent of the ordering of block copolymers in cylindrical confinement. Starting from this analogy, Leibler's theory of microphase separation in block copolymer melts is generalized to derive a description of the system in the weak segregation limit.

Conformational studies of bottle-brush polymers absorbed on a flat solid surface.

The adsorption of a bottle-brush polymer end-grafted with one chain end of its backbone to a flat substrate surface is studied by Monte Carlo simulation of a coarse-grained model, that previously has been characterized in the bulk, assuming a dilute solution under good solvent conditions. Applying the bond fluctuation model on the simple cubic lattice, we vary the backbone chain length N(b) from N(b)=67 to N(b)=259 effective monomeric units, the side chain length N from N=6 to N=48, and set the grafting density to σ=1, i.e.

How to define variation of physical properties normal to an undulating one-dimensional object.

One-dimensional flexible objects are abundant in physics, from polymers to vortex lines to defect lines and many more. These objects structure their environment and it is natural to assume that the influence these objects exert on their environment depends on the distance from the line object. But how should this be defined? We argue here that there is an intrinsic length scale along the undulating line that is a measure of its stiffness (i.

Phase transitions of a single polymer chain: A Wang-Landau simulation study.

A single flexible homopolymer chain can assume a variety of conformations which can be broadly classified as expanded coil, collapsed globule, and compact crystallite. Here we study transitions between these conformational states for an interaction-site polymer chain comprised of N=128 square-well-sphere monomers with hard-sphere diameter sigma and square-well diameter lambdasigma. Wang-Landau sampling with bond-rebridging Monte Carlo moves is used to compute the density of states for this chain and both canonical and microcanonical analyses are used to identify and characterize phase transitions in this finite size system.