Complex Macromolecular Systems Research Articles

Assessment of Solubility Behavior of a Copolymer in Supercritical CO2 and Organic Solvents: Neural Network Prediction and Statistical Analysis.

In the industrial sector, understanding the behavior of block copolymers in supercritical solvents is crucial. While qualitative agreement with polymer solubility curves has been evaluated using complex theoretical models in many cases, quantitative predictions remain challenging. This study aimed to create a rapid and accurate artificial neural network (ANN) model to predict the lower critical solubility and upper critical solubility space of an atypical block copolymer, poly(styrene-co-octafluoropentyl methacrylate) (PSOM), in different supercritical solvent systems over a wide range of temperatures (51.75-182.05 °C) and high pressure (3.28-200.86 MPa). The experimental data set used in this study included one copolymer, five supercritical solvents, one cosolvent, and one initiator. It consisted of seven unique copolymer-solvent combinations (252 cloud point pressures) used to predict the model quantitatively and qualitatively. To predict the PSOM-solvent interactions, the study considered two different input systems: a six-variable system, a five-variable system, and one target output. Initially, we used a three-layer feed-forward neural network to select the best learning algorithm (Levenberg-Marquardt) from 14 different algorithms, considering one sample PSOM-solvent system. Then, the network topology was optimized by varying hidden neuron numbers from 2 to 80 for all seven PSOM-solvent combination systems. The predicted cloud point pressures were in excellent agreement with the experimental cloud point pressures, confirming the model's accuracy. It is clear from the results of a minimum mean square error (≤1.90 × 10-27) and maximum linear regression R 2 (≥0.99) during training, validation, and testing of all the data sets. Further, the ANN model accuracy was tested by statistical analysis, confirming the model's ability to accurately capture the miscibility regions of polymers, enabling efficient processing of various polymer materials. This data-driven approach facilitates the prediction of coexistence curves for other polymers and complex macromolecular systems.

Role of Conformational Entropy in Complex Macromolecular Systems

Role of Conformational Entropy in Complex Macromolecular Systems

Mechanistic Insights into the Long-range Allosteric Regulation of KRAS Via Neurofibromatosis Type 1 (NF1) Scaffold Upon SPRED1 Loading

Allosteric regulation is the most direct and efficient way of regulating protein function, wherein proteins transmit the perturbations at one site to another distinct functional site. Deciphering the mechanism of allosteric regulation is of vital importance for the comprehension of both physiological and pathological events in vivo as well as the rational allosteric drug design. However, it remains challenging to elucidate dominant allosteric signal transduction pathways, especially for large and multi-component protein machineries where long-range allosteric regulation exits. One of the quintessential examples having long-range allosteric regulation is the ternary complex, SPRED1–RAS–neurofibromin type 1 (NF1, a RAS GTPase–activating protein), in which SPRED1 facilitates RAS–GTP hydrolysis by interacting with NF1 at a distal, allosteric site from the RAS binding site. To address the underlying mechanism, we performed extensive Gaussian accelerated molecular dynamics simulations and Markov state model analysis of KRAS–NF1 complex in the presence and absence of SPRED1. Our findings suggested that SPRED1 loading allosterically enhanced KRAS–NF1 binding, but hindered conformational transformation of the NF1 catalytic center for RAS hydrolysis. Moreover, we unveiled the possible allosteric pathways upon SPRED1 binding through difference contact network analysis. This study not only provided an in-depth mechanistic insight into the allosteric regulation of KRAS by SPRED1, but also shed light on the investigation of long-range allosteric regulation among complex macromolecular systems.

Thermal Conductivity of Semicrystalline Polymer Networks: Crystallinity or Cross-Linking?

Understanding the heat flow in polymers is at the onset of many developments in designing advanced functional materials. Here, however, amorphous linear polymers usually exhibit a very low thermal conductivity κ, often hindering their broad applications. In this context, two common routes to increase κ are via semicrystallinity and cross-linking. It can therefore be inferred that the combination of these two effects may result in a further increase of κ with respect to the systems where only one of these two effects is important. Using molecular dynamics simulations, we investigate κ in semicrystalline polymer networks. Contrary to a priori understanding, we show that a combination of cross-linking and crystallinity does not always increase κ. Instead, a delicate competition between the lattice periodicity, the cross-linker types, and the bond density dictates the tunability of κ in these complex macromolecular systems. These results are also compared with the existing experiments.

Advances in experimental studies of internal motions of non-linear macromolecular systems in solutions

The internal motions of macromolecular systems in solutions are closely related with the microscopic relaxation and macroscopic rheological behavior, therefore, this topic has been extensively studied both theoretically and experimentally. It is well-known that for a flexible or semi-flexible macromolecules with sufficient large chain size, there are two basic modes of motions in dilute solution, namely, translational motion of center of mass of a chain, and internal motions of segments with respect to the center of mass of a chain. In the past few decades, the advancement in characterization and analysis methods make it possible to distinguish both modes of motions experimentally. Although a significant experimental progress has been achieved to understand the intrachain dynamics and test the predictions by classical theory, previously published reviews have been only focused on the linear chain system with the simplest architecture feature. Herein, we aim to provide a comprehensive review on the internal motions of complex macromolecular systems of non-linear architecture. The review is organized as follows: firstly, we will briefly discuss the theoretical and experimental background of internal motions of linear chains; secondly, we will introduce the research progress of internal motions of typical complex macromolecular systems, including hyperbranched polymers, microgels/macrogels, graft polymers and polymeric assemblies/clusters; in the end, a few unresolved questions are enumerated for future studies. We hope this review can afford useful information for understanding the intrachain dynamics of complex macromolecular systems and stimulate the development of universal theory for these systems.

Synthetic Antibodies Detect Distinct Cellular States of Chromosome Passenger Complex Proteins

High performance affinity reagents are essential tools to enable biologists to profile the cellular location and composition of macromolecular complexes undergoing dynamic reorganization. To support further development of such tools, we have assembled a high-throughput phage display pipeline to generate Fab-based affinity reagents that target different dynamic forms of a large macromolecular complex, using the Chromosomal Passenger Complex (CPC), as an example. The CPC is critical for the maintenance of chromosomal and cytoskeleton processes during cell division. The complex contains 4 protein components: Aurora B kinase, survivin, borealin and INCENP. The CPC acts as a node to dynamically organize other partnering subcomplexes to build multiple functional structures during mitotic progression. Using phage display mutagenesis, a cohort of synthetic antibodies (sABs) were generated against different domains of survivin, borealin and INCENP. Immunofluorescence established that a set of these sABs can discriminate between the form of the CPC complex in the midbody versus the spindle. Others localize to targets, which appear to be less organized, in the nucleus or cytoplasm. This differentiation suggests that different CPC epitopes have dynamic accessibility depending upon the mitotic state of the cell. An Immunoprecipitation/Mass Spectrometry analysis was performed using sABs that bound specifically to the CPC in either the midbody or MT spindle macromolecular assemblies. Thus, sABs can be exploited as high performance reagents to profile the accessibility of different components of the CPC within macromolecular assemblies during different stages of mitosis suggesting this high throughput approach will be applicable to other complex macromolecular systems.

Remotely controllable supramolecular rotor mounted inside a porphyrinic cage

Remotely controllable supramolecular rotor mounted inside a porphyrinic cage

30 Years of Macromolecular Theory and Simulations

30 Years of <i>Macromolecular Theory and Simulations</i>

ЦИФРОВЫЕ ТЕХНОЛОГИИ ПРИ АНАЛИЗЕ СОСТОЯНИЯ ДРЕВЕСНЫХ РАСТЕНИЙ

The state of woody plants determines the viability of forests and environmental safety in urban environments largely. Therefore, scientific studies of the tree response as a complex biosystem on environmental factors changes are especially relevant due to the growing threat of environmental disasters (environmental pollution, active felling, etc.). Many modern methods for assessing the state of such complex macromolecular systems are verbal in nature due to the lack of non-destructive testing methods with controlled accuracy. The shortage of experimental measurements retards the development of modeling the state of trees and, consequently, the development of methods for predicting their response on the influence of external factors. The development of digital technology can change the current state of affairs in this sphere. In the report, within the framework of a systematic approach, the possibility of using digital technologies at analyzing the response of the state of woody plants on environmental factors changes has analyzed. The results of studying the flow of salt solutions in the xylem of tree trunks are presented to solve the problem. Based on experimental data, models are proposed that can become the basis of calculation systems for analyzing the state parameters of woody plants and predicting the occurrence of environmental disasters.

Optical Tweezers Microrheology Maps the Dynamics of Strain-Induced Local Inhomogeneities in Entangled Polymers.

Optical tweezers microrheology (OTM) offers a powerful approach to probe the nonlinear response of complex soft matter systems, such as networks of entangled polymers, over wide-ranging spatiotemporal scales. OTM can also uniquely characterize the microstructural dynamics that lead to the intriguing nonlinear rheological properties that these systems exhibit. However, the strain in OTM measurements, applied by optically forcing a microprobe through the material, induces network inhomogeneities in and around the strain path, and the resultant flow field complicates the measured response of the system. Through a robust set of custom-designed OTM protocols, coupled with modeling and analytical calculations, we characterize the time-varying inhomogeneity fields induced by OTM measurements. We show that homogenization following strain does not interfere with the intrinsic stress relaxation dynamics of the system, rather it manifests as an independent component in the stress decay, even in highly nonlinear regimes such as with the microrheological large-amplitude-oscillatory-shear (MLAOS) protocols we introduce. Our specific results show that Rouse-like elastic retraction, rather than disentanglement and disengagement, dominates the nonlinear stress relaxation of entangled polymers at micro- and mesoscales. Thus, our study opens up possibilities of performing precision nonlinear microrheological measurements, such as MLAOS, on a wide range of complex macromolecular systems.

MicroRNA Expression is Associated with Sepsis Disorders in Critically Ill Polytrauma Patients.

A critically ill polytrauma patient is one of the most complex cases to be admitted to the intensive care unit, due to both the primary traumatic complications and the secondary post-traumatic interactions. From a molecular, genetic, and epigenetic point of view, numerous biochemical interactions are responsible for the deterioration of the clinical status of a patient, and increased mortality rates. From a molecular viewpoint, microRNAs are one of the most complex macromolecular systems due to the numerous modular reactions and interactions that they are involved in. Regarding the expression and activity of microRNAs in sepsis, their usefulness has reached new levels of significance. MicroRNAs can be used both as an early biomarker for sepsis, and as a therapeutic target because of their ability to block the complex reactions involved in the initiation, maintenance, and augmentation of the clinical status.

Relay Conjugation of Living Metathesis Polymers.

The covalent coupling of complex macromolecules is a modern challenge in both chemistry and biology. The development of efficient and chemoselective methods for polymer coupling and functionalization are increasingly important for designing new advanced materials and interfacing with biochemical systems. Herein, we present a new strategy to directly conjugate living polymers prepared using ring-opening metathesis polymerization (ROMP) to both small molecules and synthetic macromolecules. Central to this methodology is a terminal alkyne that serves as a directing group to promote a rapid, intramolecular reaction with an otherwise unreactive olefin. This highly chemoselective relay conjugation is compatible with a range of monomer families and uses a bench-stable enyne motif that can be easily introduced to functional targets. The rapid rate of the conjugation reaction paves the way for greatly streamlined construction of complex macromolecular systems derived from metathesis polymerization techniques without the need for specialized equipment.

Structure of flexible proteins using scattering and simulation

Conformational flexibility, manifested as transitions among multiple states accessible to a macromolecular system, is of critical importance to function. Understanding the solution conformational flexibility is challenging: crystallography is inappropriate for this and the application of NMR to large complexes is challenging due to the difficulty in assigning NMR correlations. We have characterized the structure of two flexible proteins: the intrinsically disordered terminal of the c-Src kinase and the Cel7A cellulase. We combined small-angle scattering experiments and molecular dynamics simulations and determined the ensemble of conformations the two proteins sample. We discuss how the integration of scattering and molecular simulations can obtain a complete picture of the relationship between flexible structure and function in complex macromolecular systems. Support or Funding Information “Integrating Small-Angle Neutron Scattering with Molecular Simulation to Determine Structural Ensembles of Complex Biological Systems”. U.S. Department of Energy - Director's Research and Development (LDRD). “Dynamic Visualization of Lignocellulose Degradation by Integration of Neutron Scattering Imaging and Computer Simulation”.U.S. Department of Energy, Office of Biological and Environmental Research (BER) Genomic Science Program. A cellulase (orange) hydrolyzing cellulose (green) in the presence of lignin (brown). This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Simultaneous Determination of Protein Structure and Dynamics Using Cryo-Electron Microscopy

Cryo-electron microscopy is rapidly emerging as a powerful technique to determine the structures of complex macromolecular systems elusive to other techniques. Because many of these systems are highly dynamical, characterizing their movements is also a crucial step to unravel their biological functions. To achieve this goal, we report an integrative modeling approach to simultaneously determine structure and dynamics of macromolecular systems from cryo-electron microscopy density maps. By quantifying the level of noise in the data and dealing with their ensemble-averaged nature, this approach enables the integration of multiple sources of information to model ensembles of structures and infer their populations. We illustrate the method by characterizing structure and dynamics of the integral membrane receptor STRA6, thus providing insights into the mechanisms by which it interacts with retinol binding protein and translocates retinol across the membrane.

Ultra-Coarse-Grained Models Allow for an Accurate and Transferable Treatment of Interfacial Systems.

Interfacial systems are fundamentally important in many processes. However, constructing coarse-grained (CG) models for such systems is a significant challenge due to their inhomogeneous nature. This problem is made worse due to the generally nontransferable nature of the interactions in CG models across different phases. In this paper, we address these challenges by systematically constructing ultra-coarse-grained (UCG) models for interfaces, in which the CG sites are allowed to have internal states. We find that a multiscale coarse-grained (MS-CG) representation of a single CG site model fails to identify the directionality of a molecule and is unable to reproduce the correct phase coexistence for aspherical molecules. In contrast with conventional MS-CG models, the UCG methodology allows chemical and environmental changes to be captured by modulating the interactions between internal states. In this work, we design the internal states to depend on local particle density to distinguish different phases in liquid/vapor or liquid/liquid interfaces. These UCG models are able to capture phase coexistence and recapitulate structures, notably at state points in which the MS-CG method yields poor results. Interestingly, effective pairwise forces and potentials from the UCG models are almost identical to those of the bulk liquids that correspond to each phase, indicating that the UCG approach can provide transferable interactions. This approach is expected to be applicable to other systems that exhibit phase coexistence and also to complex macromolecular systems by modulating interactions based on local density or other order parameters to unravel the complex nature underlying heterogeneous system boundaries.

David Beratan wins Florida Award

David Beratan, the R.J. Reynolds Professor of Chemistry at Duke University, has won the 2017 Florida Award, presented by the ACS Florida Section. The award recognizes leadership and contributions toward the advancement of the profession of chemistry. The honor is bestowed to a chemist working in the southeastern U.S. Beratan is being recognized for his contributions to theoretical biophysics and biophysical chemistry. His research group focuses on developing theoretical approaches to understand the function of complex molecular and macromolecular systems.

Metadynamic metainference: Enhanced sampling of the metainference ensemble using metadynamics.

Accurate and precise structural ensembles of proteins and macromolecular complexes can be obtained with metainference, a recently proposed Bayesian inference method that integrates experimental information with prior knowledge and deals with all sources of errors in the data as well as with sample heterogeneity. The study of complex macromolecular systems, however, requires an extensive conformational sampling, which represents a separate challenge. To address such challenge and to exhaustively and efficiently generate structural ensembles we combine metainference with metadynamics and illustrate its application to the calculation of the free energy landscape of the alanine dipeptide.

Interview with Daan Frenkel, Boltzmann Medallist 2016 : Simulating soft matter through the lens of statistical mechanics.

Daan Frenkel has been awarded the most important prize in the field of statistical mechanics, the 2016 Boltzmann Medal, named after the Austrian physicist and philosopher Ludwig Boltzmann. The award recognises Frenkel's seminal contributions to the statistical-mechanical understanding of the kinetics, self-assembly and phase behaviour of soft matter. The honour recognises Frenkel's highly creative large-scale simulations of soft matter capable of explaining the self-assembly of complex macromolecular systems, colloidal and biomolecular systems. Frenkel is Professor of Theoretical Chemistry at the University of Cambridge, UK and has been Editor in Chief of EPJE between 2010 and 2014. The award will be given to both Frenkel and his French colleague Yves Pomeau, during the StatPhys Conference on 20th July 2016 in Lyon, France. In this interview with Sabine Louët, Frenkel gives his views on statistical physics, which has become more relevant than ever for interdisciplinary research. He also offers some pearls of wisdom for the next generation Statistical Mechanics experts.

Multiscale approach for the construction of equilibrated all-atom models of a poly(ethylene glycol)-based hydrogel.

A multiscale modeling approach is presented for the efficient construction of an equilibrated all-atom model of a cross-linked poly(ethylene glycol) (PEG)-based hydrogel using the all-atom polymer consistent force field (PCFF). The final equilibrated all-atom model was built with a systematic simulation toolset consisting of three consecutive parts: (1) building a global cross-linked PEG-chain network at experimentally determined cross-link density using an on-lattice Monte Carlo method based on the bond fluctuation model, (2) recovering the local molecular structure of the network by transitioning from the lattice model to an off-lattice coarse-grained (CG) model parameterized from PCFF, followed by equilibration using high performance molecular dynamics methods, and (3) recovering the atomistic structure of the network by reverse mapping from the equilibrated CG structure, hydrating the structure with explicitly represented water, followed by final equilibration using PCFF parameterization. The developed three-stage modeling approach has application to a wide range of other complex macromolecular hydrogel systems, including the integration of peptide, protein, and/or drug molecules as side-chains within the hydrogel network for the incorporation of bioactivity for tissue engineering, regenerative medicine, and drug delivery applications.

Biocompatibility behavior of β–tricalcium phosphate-chitosan coatings obtained on 316L stainless steel

Biological interfaces involve the interaction of complex macromolecular systems and other biomolecules or biomaterials. Researchers have used a combination of cell, material sciences and engineering approaches to create functional biointerfaces to help improve biological functions. Materials such as hydroxyapatite (HA), β-tricalcium phosphate (β-TCP) and chitosan are important biomaterials to be used in biomedical applications such as bone-prosthesis interfaces. In this work, it was evaluated the effect of different concentrations of chitosan on the structural, electrochemical and biocompatible properties of β-tricalcium phosphate-chitosan ((β-Ca3(PO4)2)-(C6H11NO4)n) hybrid coatings. β–tricalcium phosphate-chitosan coatings were deposited on 316L stainless steel substrates applying 260 mA AC, an agitation velocity of 250 rpm, and temperature deposition of 60 °C. It was possible to obtain coatings of 600 μm of thickness. Structure and surface properties were analyzed by X-ray diffraction (XRD) and dispersive X-ray analysis (EDX). It was found that the arrangement of the β-TCP crystal lattice changed with increasing chitosan weight concentration, showing that the orthorhombic structure of β-TCP is under tensile stress. The electrochemical properties of β–tricalcium phosphate/chitosan (β-TCP–Ch) coatings were analyzed by electrochemical impedance spectroscopy (EIS). Cellular biocompatibility was determined by lactate dehydrogenase (LDH) cytotoxicity assay using primary chinese hamster ovary (CHO) cells. β-TCP–Ch coatings with chitosan concentrations up to 25% caused cytotoxic effects to only 5–10% of CHO cells. Obtained results showed the influence of chitosan in the structural, electrochemical, and biocompatible properties of AISI 316L Stainless Steel. Consequently, the electrochemical and cytotoxic behavior of β-TCP–Ch on 316L Stainless Steel indicated that the coatings might be a promising material in biomedical applications.