Here, we survey computational modeling approaches of surfactant assemblies in apolar solvents, with specific attention to differences and caveats due to the solvent environment being apolar instead of water. Surfactant assembly in apolar solvents arises via specific enthalpic interactions and weak polarity contrasts between the surfactant tails and the solvent. As a computational model construction premise, this is different from the hydrophobicity-driven surfactant assembly in aqueous solution, where the loss of solvent entropy is minimized by shielding the apolar tails from water. The difference in the driving forces leads to nonobvious challenges when using models parameterized for aqueous solutions in describing apolar solvent systems. We cover from atomistic to coarse-grained molecular modeling and mesoscale models but also continuum-scale approaches, including models of reverse micellar charge transfer. While data-based, machine learning approaches to surfactants in apolar solvents remain limited to date, perspective to their potential is provided. Finally, we offer insight to how the currently available modeling approaches that have typically been constructed for accuracy in water solutions should be used to describe accurately also surfactant assembly in apolar solvents and the considerations required.

Abstract Fungal surfaces must remain hydrophobic to enable growth, dispersal, and survival under fluctuating environmental conditions, yet the molecular basis of this property remains incompletely understood. Here, we identify fungisporins, fusahexins, and related cyclic non-ribosomal peptides (NRPs) as members of a conserved functional class of fungal metabolites, termed WAter Repellent Peptides (WARPs), that are required for fungal surface hydrophobicity. Across filamentous fungi, WARPs vary substantially in sequence and length but share conserved structural features, including cyclization, hydrophobic amino acid composition, and alternating D- and L-configurations, consistent with a flexible amphiphilic scaffold. Loss of WARP-producing non-ribosomal peptide synthetases results in rapid collapse of aerial hyphae upon water exposure, demonstrating that these peptides are required for maintenance of hydrophobic aerial structures. Using phage-display-derived antibodies, we localize WARPs to the hyphal surface, supporting their role as surface-associated structural components. Together, these findings identify a conserved NRPS-encoded peptide system that contributes to fungal hydrophobicity and establish WARPs as a broadly distributed class of surface-associated metabolites with structural function in filamentous fungi.

Here, we explore the molecular level origins of the curious temperature and time dependent assembly phase response of silk-like protein materials. Combining molecular dynamics simulations, CD and FTIR spectroscopy, as well as optical microscopy, we examine the assembly phase response of model engineered tri-block protein constructs with a middle intrinsically disordered region and folded terminal domains. We show that, the assembly phase response over a broad temperature range between 20 and 80 °C arises from strong interprotein interactions. The phase transitions are governed by the interplay of changes in the entropy of the flexible glycine-rich regions and the hydrophobic interactions between the α-helices rich in alanine (Ala). Furthermore, we observe irreversible gelation at high temperatures and during aging (time-induced gelation). Thermal gelation rises via interactions between the Ala-rich regions and subsequent formation of β-sheets that crosslink the protein network. On the other hand, the time-induced gel is formed with no notable secondary structure transitions of the middle block via percolation of the protein, which is sensitive to the dimerizing interactions of the terminal domains. Overall, the significance of this work is that we identify time as a separate design variable from the molecular level characteristics and solution conditions of the silk-like protein gels, and extract assembly guidelines for the gel formation and its characteristics.

Ion-specific effects on aqueous solvation of monovalent counter ions, Na + ${^+ }$ , K + ${^+ }$ , Cl - ${^- }$ , and Br - ${^- }$ , and two model polyelectrolytes (PEs), poly(styrene sulfonate) (PSS) and poly(diallyldimethylammonium) (PDADMA) were here studied with ab initio molecular dynamics (AIMD) and classical molecular dynamics (MD) simulations based on the OPLS-aa force-field which is an empirical fixed point-charge force-field. Ion-specific binding to the PE charge groups was also characterized. Both computational methods predict similar response for the solvation of the PEs but differ notably in description of ion solvation. Notably, AIMD captures the experimentally observed differences in Cl - ${^- }$ and Br - ${^- }$ anion solvation and binding with the PEs, while the classical MD simulations fail to differentiate the ion species response. Furthermore, the findings show that combining AIMD with the computationally less costly classical MD simulations allows benefiting from both the increased accuracy and statistics reach.

Crystalline nanocellulose is widely used for example, in the paper-making and food industries, as support matrix material or reinforcement of polymer materials, but also in drug carrier and nanomedicine applications. Interestingly, aqueous solutions of cellulose are extremely sensitive to small amounts of added salt yet mere considerations of charge screening leave open questions regarding the mechanisms, especially for unmodified cellulose in aqueous solutions. Here, we map NaCl ion distributions and the effect of added NaCl salt on the hydration of I β cellulose nanocrystal (CNC) surfaces by atomistic detail molecular dynamics simulations with explicit water solvent. The simulations reveal the dependency of the hydration layers of the six surfaces of CNCs on the ions, as well as NaCl ion binding sites, and preferences in terms of binding free energy for the ions near CNC surfaces at different NaCl concentrations. We discuss the modelling results against our prior rheology characterization of cellulose solutions. Together, the results indicate that the high sensitivity of cellulose aqueous solutions to added salt rises from the ions near the surface changing locally the ordering and structure of the hydration layers of the CNC surfaces. The revealed mechanism of salt-induced viscosity changes in cellulose aqueous solutions allows advanced design of gelling CNC systems for various end uses and may also guide tuning cellulose interactions by different solvent environments.

The materials characteristics of natural wood but also the properties of artificial cellulose/hemicellulose-based wood-inspired composite materials result from the molecular level organization and interactions between cellulose, hemicellulose, and lignin. Here, we use atomistic detail molecular dynamics simulations to examine the adsorption of model lignin-carbohydrate complexes (LCCs) consisting of a glucomannan polysaccharide chain with differing lignin fragment linkages to the crystalline facets of cellulose nanocrystals. The findings show that on crystalline cellulose surfaces exceeding in surface dimensions the length of the adsorbed hemicellulose chain, the LCCs can adopt orientations both parallel and perpendicular to the surface chains with response depending on the crystalline facet. The observation of perpendicular orientations is unexpected, as previous molecular level modelling studies systematically report parallel LCC adsorption orientation, however on cellulose interfaces modelling the narrow natural wood cellulose fibrils. Here, the perpendicular adsorption orientation is stabilized by extensive hydrogen bonding and adsorption of the hemicellulose chain with negligible chain bending. Overall, the results show that component dimensions (hemicellulose chain length vs cellulose crystalline surface dimensions) combined with understanding the differences of adsorption response at the difference crystal facets are crucial in understanding wood-inspired materials.

Polyelectrolyte complexes (PECs) have attracted considerable attention owing to their unique physicochemical properties and potential applications as smart materials. Herein, the glass transitions of PECs solvated with varying alcohols are investigated in poly(diallyldimethylammonium)/poly(acrylic acid) (PDADMA/PAA) complexes by using modulated differential scanning calorimetry (MDSC). Solvents with one or two hydroxyl groups are selected to examine the effect of PAA-solvent interactions on the glass transition temperature (T g). Except for glycerol, all alcohol solvents yield PECs with detectable T g's and plasticization behavior. Furthermore, a linear relationship for 1/T g and the natural logarithm of the number of hydroxyl groups to intrinsic ion pair ratio [ln(n hydroxyl/n intrinsic-ion-pair)] is found. This result is significant because prior work demonstrated the relationship only for water and no other solvents. All-atom molecular dynamics (MD) simulations analyze the ability of the solvent to form hydrogen bonds via the solvent's OH groups to the PAA, revealing that the solvent molecule size and available hydroxyl groups govern the change in the glass transition. Overall, the clear dependence of a PEC's glass transition on the solvent's chemical structure provides a simple guideline for predicting their relationship.

Condensates are molecular assemblies that are formed through liquid-liquid phase separation and play important roles in many biological processes. The rational design of condensate formation and their properties is central to applications, such as biosynthetic materials, synthetic biology, and for understanding cell biology. Protein engineering is used to make a triblock structure with varying terminal blocks of folded proteins on both sides of an intrinsically disordered mid-region. Dissociation constants are determined in the range of micromolar to millimolar for a set of proteins suitable for use as terminal blocks. Varying the weak dimerization of terminal blocks leads to an adjustable tendency for condensate formation while keeping the intrinsically disordered region constant. The dissociation constants of the terminal domains correlate directly with the tendency to undergo liquid-liquid phase separation. Differences in physical properties, such as diffusion rate are not directly correlated with the strength of dimerization but can be understood from the properties and interplay of the constituent blocks. The work demonstrates the importance of weak interactions in condensate formation and shows a principle for protein design that will help in fabricating functional condensates in a predictable and rational way.

Future sustainable materials based on designer biomolecules require control of the solution assembly, but also interfacial interactions. Alcohol treatments of protein materials are an accessible means to this, making understanding of the process at the molecular level of seminal importance. We focus here on the influence of ethanol on spidroins, the main proteins of silk. By large-scale atomistically detailed molecular dynamics (MD) simulations and interconnected experiments, we characterize the protein aggregation, secondary structure changes, molecular level origins of them, and solvation environment changes for the proteins, as induced by ethanol as a solvation additive. The MD and circular dichoroism (CD) findings jointly show that ethanol promotes ordered structure in the protein molecules, leading to an increase of helix content and turns but also increased aggregation, as revealed by dynamic light scattering (DLS) and light microscopy. The structural changes correlate at the molecular level with increased intramolecular hydrogen bonding. The simulations reveal that polar amino acids, such as glutamine and serine, are most influenced by ethanol, whereas glycine residues are most prone to be involved in the ethanol-induced secondary structure changes. Furthermore, ethanol engages in interactions with the hydrophobic alanine-rich regions of the spidroin, significantly decreasing the hydrophobic interactions of the protein with itself and its surroundings. The protein solutes also change the microstructure of water/ethanol mixtures, essentially decreasing the level of larger local clustering. Overall, the work presents a systematic characterization of ethanol effects on a widely used, common protein type, spidroins, and generalizes the findings to other intrinsically disordered proteins by pinpointing the general features of the response. The results can aid in designing effective alcohol treatments for proteins, but also enable design and tuning of protein material properties by a relatively controllable solvation handle, the addition of ethanol.

Deep eutectic solvents (DESs) are multi-component solvents appearing in a broad range of applications. The next necessary step for the development of new DESs is understanding the molecular mechanisms of DES formation and the interactions that determine its structure and properties. In this work, we use multiscale simulations supported by experiments to investigate the detailed structure and properties of polymerizable DESs based on choline chloride and acrylic acid as a basis for creating inks for 3D printing. Thermodynamic and structural analyses show the physical mechanisms of DES formation in these materials: due to the significant size difference between the acrylic acid and choline ions, and favorable interactions between acrylic acid and the Cl- ions, the acrylic acid molecules are able to incorporate into the free spaces of the first coordination shells of the Cl- ions. As a consequence, the mixture has less volume than its individual components and this excess volume determines the negative value of the enthalpy of mixing. Structurally, the mixture is a network with the Cl- ions as nodes connecting the other DES components. This was confirmed by both the FTIR experiments and the atomistic MD simulations. The calculations show the necessity of correct accounting of excess enthalpy and entropy for determining DESs structures and other properties.(c) 2022 Elsevier B.V. All rights reserved.

Electrostatic interactions have a determining role in the conformational and dynamic behavior of polyelectrolyte molecules. In this study, anionic polyelectrolyte molecules, poly(glutamic acid) (PGA) and poly(aspartic acid) (PASA), in a water solution with the most commonly used K+ or Na+ counterions, were investigated using atomistic molecular dynamics (MD) simulations. We performed a comparison of seven popular force fields, namely AMBER99SB-ILDN, AMBER14SB, AMBER-FB15, CHARMM22*, CHARMM27, CHARMM36m and OPLS-AA/L, both with their native parameters and using two common corrections for overbinding of ions, the non-bonded fix (NBFIX), and electronic continuum corrections (ECC). These corrections were originally introduced to correct for the often-reported problem concerning the overbinding of ions to the charged groups of polyelectrolytes. In this work, a comparison of the simulation results with existing experimental data revealed several differences between the investigated force fields. The data from these simulations and comparisons with previous experimental data were then used to determine the limitations and strengths of these force fields in the context of the structural and dynamic properties of anionic polyamino acids. Physical properties, such as molecular sizes, local structure, and dynamics, were studied using two types of common counterions, namely potassium and sodium. The results show that, in some cases, both the macroion size and dynamics depend strongly on the models (parameters) for the counterions due to strong overbinding of the ions and charged side chain groups. The local structures and dynamics are more sensitive to dihedral angle parameterization, resulting in a preference for defined monomer conformations and the type of correction used. We also provide recommendations based on the results.

Deep eutectic solvents (DESs) are one of the most rapidly evolving types of solvents, appearing in a broad range of applications, such as nanotechnology, electrochemistry, biomass transformation, pharmaceuticals, membrane technology, biocomposite development, modern 3D-printing, and many others. The range of their applicability continues to expand, which demands the development of new DESs with improved properties. To do so requires an understanding of the fundamental relationship between the structure and properties of DESs. Computer simulation and machine learning techniques provide a fruitful approach as they can predict and reveal physical mechanisms and readily be linked to experiments. This review is devoted to the computational research of DESs and describes technical features of DES simulations and the corresponding perspectives on various DES applications. The aim is to demonstrate the current frontiers of computational research of DESs and discuss future perspectives.

Publications showing the prospects of combining computer simulation with atomic force microscopy in the study of polymer biological objects and materials for various purposes are analyzed. The problems that arise when these methods are used together are described. Three main directions are presented in which atomic force microscopy is used in conjunction with computer simulation: study of the surface topography of polymer materials; measurement of the force curve of the interaction of the atomic force probe with polymer structures; and determination of the energy of intermolecular interactions.

We used atomistic molecular dynamics (MD) simulations to study polyelectrolyte brushes based on anionic α,L-glutamic acid and α,L-aspartic acid grafted on cellulose in the presence of divalent CaCl2 salt at different concentrations. The motivation is to search for ways to control properties such as sorption capacity and the structural response of the brush to multivalent salts. For this detailed understanding of the role of side-chain length, the chemical structure and their interplay are required. It was found that in the case of glutamic acid oligomers, the longer side chains facilitate attractive interactions with the cellulose surface, which forces the grafted chains to lie down on the surface. The additional methylene group in the side chain enables side-chain rotation, enhancing this effect. On the other hand, the shorter and more restricted side chains of aspartic acid oligomers prevent attractive interactions to a large degree and push the grafted chains away from the surface. The difference in side-chain length also leads to differences in other properties of the brush in divalent salt solutions. At a low grafting density, the longer side chains of glutamic acid allow the adsorbed cations to be spatially distributed inside the brush resulting in a charge inversion. With an increase in grafting density, the difference in the total charge of the aspartic and glutamine brushes disappears, but new structural features appear. The longer sides allow for ion bridging between the grafted chains and the cellulose surface without a significant change in main-chain conformation. This leads to the brush structure being less sensitive to changes in salt concentration.

Investigation of the effect of CaCl2 salt on conformations of two anionic poly(amino acids) with different side chain lengths, poly-(α-l glutamic acid) (PGA) and poly-(α-l aspartic acid) (PASA), was performed by atomistic molecular dynamics (MD) simulations. The simulations were performed using both unbiased MD and the Hamiltonian replica exchange (HRE) method. The results show that at low CaCl2 concentration adsorption of Ca2+ ions lead to a significant chain size reduction for both PGA and PASA. With the increase in concentration, the chains sizes partially recover due to electrostatic repulsion between the adsorbed Ca2+ ions. Here, the side chain length becomes important. Due to the longer side chain and its ability to distance the charged groups with adsorbed ions from both each other and the backbone, PGA remains longer in the collapsed state as the CaCl2 concentration is increased. The analysis of the distribution of the mineral ions suggests that both poly(amino acids) should induce the formation of mineral with the same structure of the crystal cell.

An environment-friendly method for obtaining cellulose nanocrystals (CNC) using deep eutectic solvents (DES) was developed. Formation of highly crystalline CNC with average particle dimensions 20 × 100 × 700 nm was confirmed with SEM and AFM. Molecular dynamics simulations demonstrated that the hydrogen bond interactions of the cellulose hydroxyl groups with the urea C=O group and with the chloride ions were the key factors of the destruction of MCC particles in the process of solvation. The type of cellulose crystal structure (Iβ) and the high degree of crystallinity (about 80% according to Segal method) were preserved during treatment with DES. The ability of the prepared CNC to act as a reinforcing filler was tested by introduction of them into the chitosan-based films plasticized with DES. It was found that addition of 2 wt% of CNC led to an increase in the strength of the films from 11.4 up to 20.4 MPa with a simultaneous increase in the elongation at break.

Overbinding of ions is a common and well-known problem in classical molecular dynamics simulations. One of its main causes is the absence of electronic polarizability in the force fields. The current approaches for minimizing overbinding typically either retain the original charges and use an ad hoc readjustment of the Lennard-Jones parameters as done in the nonbonded fix (NBFIX) approach or rescale the charges using a theoretical framework. The goal in the latter is to include shielding produced by the missing electronic polarizability as done in the electronic continuum correction (ECC) approach. NBFIX and ECC are the most common corrections, and we compare their performance to the default parameterizations provided by five different commonly used biomolecular force fields, OPLS-AA/L, CHARMM27, CHARMM36m, CHARMM22*, and AMBER99SB-ILDN. As test systems, we use poly-α,l-glutamic and poly-α,l-aspartic amino acid molecules in explicit water together with Na+ and K+ counterions. We demonstrate that the different force fields yield results that are not only quantitatively but also qualitatively different. The resulting structures of the macroions depend strongly on the model for ions. NBFIX corrections alleviate the problem of overbinding, resulting in extended peptides. The ECC corrections depend nontrivially on the original underlying model, and despite being based on a theoretical framework, they cannot always solve the problem.

Cellulose can be phosphorylated to produce organic matrices with highly adsorptive properties for, e.g., biocompatible materials for biomedical applications. We focus on the effects of phosphorylation of surfaces of crystalline nanocellulose and, in particular, on the competitive adsorption of mono- and divalent cations (Na+ and Ca2+) typically contained in mineralizing salt mixtures using all-atom molecular dynamics (MD) simulations. Phosphorylation was applied at 12% and 25% both in water and CaCl2 solutions. Our main result shows that Na+ and Ca2+ cations are concentrated in different interfacial layers with Na+ ions penetrating much closer to the surface. This behavior cannot be described by the Poisson-Boltzmann theory or implicit solvent simulations. Our analysis shows that the physical origin of this observation is due to a balance between the electrostatic interactions and hydration free energy associated with the ions. Adsorption levels of the different ions also respond differently to changes in the degree of phosphorylation. We show that the number of adsorbed Na+ ions per phosphate group increases whereas the number of adsorbed Ca2+ ions decreases with an increasing degree of phosphorylation (or when the number of binding sites increases). The decrease in the number of adsorbed Ca2+ ions can be explained by an increasing "charge-charge" repulsion between the Ca2+ ions attracted by the charged surface. Importantly, our results demonstrate the existence of an optimum degree of phosphorylation in terms of adsorbed Ca2+ ions and can be used as a guideline in materials design, for example, when choosing the cellulose matrix or with other similarly structured biomolecular and polymer surfaces.

We present results from all-atom molecular dynamics simulations for the structural properties of oligomeric lactic acid chains (OLA) grafted to the surface of cellulose nanocrystals (CNCs) and immersed in the melt of polylactic acid (PLA). Earlier, we have found that the distribution of free ends of OLA molecules is bimodal [Glova et al., Polym. Int., 2016, 65(8), 892]. The results cannot be explained within the standard picture of uncharged polymer brushes exposed to the melt of a chemically identical polymer. Although the oligomeric brushes of the OLA chains are uncharged, they have partial polarization charges producing a non-zero dipole moment of the monomeric chain unit. We study the influence of partial charges on the structure of the layer of OLA chains grafted to the CNC surface. A detailed analysis of the conformations of the grafted chains shows that interaction of partial charges in the models causes bending of the OLA molecules toward the cellulose surface, forming a hairpin structure. The observed separation of the grafted chains into two populations increases with grafting density. We demonstrate that hydrogen bonds can be formed between the free ends of the grafted chains and the CNC surface, but they do not affect the brush structure significantly. Thus, dipole-dipole interactions turn out to be the key factor governing the unusual conformations of grafts.