Size Of Side Chain Research Articles

A Simple Binary Supramolecular Co-Assembly Platform for Enhanced Tumor Imaging and Therapy.

The primary challenges in tumor imaging and therapy revolve around improving targeting efficiency, enhancing probe/drug delivery efficacy, and minimizing off-target signals and toxicity. Although various carriers have been developed, many are difficult to synthesize, costly, and not universally applicable. Furthermore, numerous carriers exhibit limited delivery rates in solid tumors, particularly larger nanocarriers. To address these challenges, a simple binary co-assembly drug delivery platform has been designed using the readily synthesized small molecule Cys(SEt)-Lys-CBT (CKCBT) as the self-assembly building block. CKCBT can effectively penetrate tumor cells due to its positively charged Lys side chain and small size. Upon glutathione reduction, CKCBT co-assembles with Nile red or Chlorin e6 to form nanofibers inside tumor cells. This enables their specific accumulation in tumor cells rather than normal cells and extends their exposure time, resulting in precise and enhanced tumor imaging and treatment. Hence, this uncomplicated and highly efficient binary co-assembly drug delivery platform can be easily adapted to a broad spectrum of probes and drugs, presenting a novel approach for advancing clinical diagnosis and therapy.

Polypeptoid Monomer Sequence and Chemical Composition as Independent Controls of Interfacial Tension and Elasticity at Air/Fluid Interfaces.

We use sequence-specific polypeptoids to characterize the impact of the monomer sequence on the adsorption of surface-active polymers at fluid/fluid interfaces. Sets of 36 repeat unit polypeptoids with identical chemical composition, but different sequences of hydrophobic moieties along the oligomer chain (taper, inverse taper, blocky, and evenly distributed), are designed and characterized at air/water interfaces. Polypeptoids are driven to the interfaces by decreasing the solvent quality of the aqueous solution. In situ processing of the adsorbed layers causes a collapse of polypeptoids and the formation of irreversibly adsorbed, solvent-avoiding layers at interfaces. Differences in thermodynamic properties, driven by solubility, between the collapsed structures at interfaces are studied with measurements of interfacial tension. The dilatational modulus of polypeptoid-coated interfaces is used as a proxy to probe the extent of the coil-globule collapse at the interface. The role of hydrophobicity is investigated by comparing four sequences of polypeptoids with an increased size of the hydrophilic side chains. In each set of polypeptoids, the composition of molecules, not the sequence, controls the surface concentration. The molecules are described in terms of the distribution of the hydrophobic monomers on the backbone of the polymer. Inverse taper (IT) and blocky (B) sequences of hydrophobic moieties favor the formation of highly elastic interfaces after processing, while taper (T) and distributed (D) showed lower elasticity after processing, which is achieved by replacing good solvent with poor solvent and then nonsolvent. These structures allow for the study of the impact of the chemical composition and sequence of monomers on the properties of polymer-coated interfaces.

A molecular switch in RCK2 triggers sodium-dependent activation of KNa1.1 (KCNT1) potassium channels

The Na+-activated K+ channel KNa1.1, encoded by the KCNT1 gene, is an important regulator of neuronal excitability. How intracellular Na+ ions bind and increase channel activity is not well understood. Analysis of KNa1.1 channel structures indicate that there is a large twisting of the βN-αQ loop in the intracellular RCK2 domain between the inactive and Na+-activated conformations, with a lysine (K885, human subunit numbering) close enough to potentially form a salt bridge with an aspartate (D839) in βL in the Na+-activated state. Concurrently, an aspartate (D884) adjacent in the same loop adopts a position within a pocket formed by the βO strand. In carrying out mutagenesis and electrophysiology with human KNa1.1, we found that alanine substitution of selected residues in these regions resulted in almost negligible currents in the presence of up to 40 mM intracellular Na+. The exception was D884A, which resulted in constitutively active channels in both the presence and absence of intracellular Na+. Further mutagenesis of this site revealed an amino acid size-dependent effect. Substitutions at this site by an amino acid smaller than aspartate (D884V) also yielded constitutively active KNa1.1, and D884I had Na+ dependence similar to wild-type KNa1.1, while increasing the side-chain size larger than aspartate (D884E or D884F) yielded channels that could not be activated by up to 40 mM intracellular Na+. We conclude that Na+ binding results in a conformational change that accommodates D884 in the βO pocket, which triggers further conformational changes in the RCK domains and channel activation.

Influence of Polymer Side Chain Size and Backbone Length on the Self-Assembly of Supramolecular Polymer Bottlebrushes.

Hydrogen bonds are a versatile tool for creating fibrous, bottlebrush-like assemblies of polymeric building blocks. However, a delicate balance of forces exists between the steric repulsion of the polymer chains and these directed supramolecular forces. In this work we have systematically investigated the influence of structural parameters of the attached polymers on the assembly behaviour of benzene trisurea (BTU) and benzene tris(phenylalanine) (BTP) conjugates in water. Polymers with increasing main chain lengths and different side chain sizes were prepared by reversible addition-fragmentation chain-transfer (RAFT) polymerization of hydroxyethyl acrylate (HEA), tri(ethylene glycol) methyl ether acrylate (TEGA) and oligo(ethylene glycol) methyl ether acrylate (OEGA). The resulting structures were analyzed using small angle X-ray scattering (SAXS) and transmission electron microscopy (TEM). Both BTU and BTP formed fibres with PHEA attached, but a transition to spherical morphologies was observed at degrees of polymerisation (DP) of 70 and above. Overall, the main chain length appeared to be a dominating factor in inducing morphology transitions. Increasing the side chain size generally had a similar effect but mainly impeded any aggregation as is the case of POEGA. Interestingly, BTP conjugates still formed fibres, suggesting that the stronger intermolecular interactions can compensate partially for the steric repulsion.

Deciphering functional roles of protein succinylation and glutarylation using genetic code expansion

Post-translational modifications (PTMs) dynamically regulate cellular processes. Lysine undergoes a range of acylations, including malonylation, succinylation (SucK) and glutarylation (GluK). These PTMs increase the size of the lysine side chain and reverse its charge from +1 to −1 under physiological conditions, probably impacting protein structure and function. To understand the functional roles of these PTMs, homogeneously modified proteins are required for biochemical studies. While the site-specific encoding of PTMs and their mimics via genetic code expansion has facilitated the characterization of the functional roles of many PTMs, negatively charged lysine acylations have defied this approach. Here we describe site-specific incorporation of SucK and GluK into proteins via temporarily masking their negative charge through thioester derivatives. We prepare succinylated and glutarylated bacterial and mammalian target proteins, including non-refoldable multidomain proteins. This allows us to study how succinylation and glutarylation impact enzymatic activity of metabolic enzymes and regulate protein–DNA and protein–protein interactions in biological processes from replication to ubiquitin signalling.

Molecular Dynamics Simulations of Polyelectrolyte Complexes.

Polyelectrolyte complexes (PECs) are currently of great interest due to their applications toward developing new adaptive materials and their relevance in membraneless organelles. These complexes emerge during phase separation when oppositely charged polymers are mixed in aqueous media. Peptide-based PECs are particularly useful toward developing new drug delivery methods due to their inherent biocompatibility. The underlying peptide sequence can be tuned to optimize specific material properties of the complex, such as interfacial tension and viscosity. Given their applicability, it would be advantageous to understand the underlying sequence-dependent phase behavior of oppositely charged peptides. Here, we report microsecond molecular dynamic simulations to characterize the effect of hydrophobicity on the sequence-dependent peptide conformation for model polypeptide sequences that were previously reported by Tabandeh et al. These sequences are designed with alternating chirality of the peptide backbone. We present microsecond simulations of six oppositely charged peptide pairs, characterizing the sequence-dependent effect on peptide size, degree of hydrogen bonding, secondary structure, and conformation. This analysis recapitulates sensible trends in peptide conformation and degree of hydrogen bonding, consistent with experimentally reported results. Ramachandran plots reveal that backbone conformation at the single amino acid level is highly influenced by the neighboring sequence in the chain. These results give insight into how subtle changes in hydrophobic side chain size and chirality influence the strength of hydrogen bonding between the chains and, ultimately, the secondary structure. Furthermore, principal component analysis reveals that the minimum energy structures may be subtly modulated by the underlying sequence.

Thiourea compounds with diverse hydrophobic group used as selective flotation collectors for galena

Hydrophobic group is a crucial yet underutilized component of a collector molecule. Herein we examine the flotation behaviors of thioureas with various hydrophobic groups for a galena/sphalerite mixed flotation system and compare them with sodium ethyl-xanthate (SEXT). Flotation experiments show that thiourea collectors with shorter alkyl chain and less nucleophilic amine nitrogen display better separation performance. Larger contact angles and adsorption capacities between the thiourea collectors and galena are the key to the enhanced selectivity.In the homogeneous Zn2+/Pb2+ mixed solution, thiourea collectors exhibit strong coordination ability with Pb2+, and their selectivities are noticeably higher than that of SEXT. FTIR and single crystal X-ray diffraction studies prove that thiourea collectors coordinate with metal ions through the S atom only. DFT calculations reveal how side-chain size and type can affect the selectivity.

Marine biodegradation of tailor-made polyhydroxyalkanoates (PHA) influenced by the chemical structure and associated bacterial communities

Over recent years, biodegradable polymers have been proposed to reduce environmental impacts of plastics for specific applications. The production of polyhydroxyalkanoates (PHA) by using diverse carbon sources provides further benefits for the sustainable development of biodegradable plastics. Here, we present the first study evaluating the impact of physical, chemical and biological factors driving the biodegradability of various tailor-made PHAs in the marine environment. Our multidisciplinary approach demonstrated that the chemical structure of the polymer (i.e. the side chain size for short- vs. medium-chain PHA) which was intrinsically correlated to the physico-chemical properties, together with the specificity of the biofilm growing on plastic films (i.e., the associated ‘plastisphere’) were the main drivers of the PHA biodegradation in the marine environment.

Role of Hydrophobic Amino-Acid Side-Chains in the Narrow Selectivity Filter of the CFTR Chloride Channel Pore in Conductance and Selectivity.

Cystic fibrosis is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel. Structural analysis of CFTR has identified a narrow, hydrophobic region close to the extracellular end of the open channel pore that may function as a selectivity filter. The present study combines comprehensive mutagenesis of hydrophobic amino-acid side-chains within the selectivity filter with functional evaluation of channel Cl- conductance and anion selectivity. Among these hydrophobic amino-acids, one (F337) appears to play a dominant role in determining both conductance and selectivity. Anion selectivity appears to depend on both side-chain size and hydrophobicity at this position. In contrast, conductance is disrupted by all F337 mutations, suggesting that unique interactions between permeating Cl- ions and the native phenylalanine side-chain are important for conductance. Surprisingly, a positively charged lysine side-chain can be substituted for several hydrophobic residues within the selectivity filter (including F337) with only minor changes in pore function, arguing against a crucial role for overall hydrophobicity. These results suggest that localized interactions between permeating anions and amino-acid side-chains within the selectivity filter may be more important in determining pore functional properties than are global features such as overall hydrophobicity.

At the outer part of the active site in Trypanosoma cruzi glucokinase: The role of phenylalanine 337

The hole mutagenesis approach was used to interrogate the importance of F337 in Trypanosoma cruzi glucokinase (TcGlcK) in order to understand the complete set of binding interactions that are made by d-glucosamine analogue inhibitors containing aromatic tail groups that can extend to the outer part of the active site. An interesting inhibitor of this analogue class includes 2-N-carboxybenzyl-2-deoxy-d-glucosamine (CBZ-GlcN), which exhibits strong TcGlcK binding with a Ki of 710 nM. The residue F337 is found at the outer part of the active site that stems from the second protein subunit of the homodimeric assembly. In this study, F337 was changed to leucine and alanine so as to diminish phenylalanine's side chain size and attenuate intermolecular interactions in this region of the binding cavity. Results from enzyme – inhibitor assays revealed that the phenyl group of F337 made dominant hydrophobic interactions with the phenyl group of CBZ-GlcN as opposed to π – π stacking interactions. Moreover, enzymatic activity assays and X-ray crystallographic experiments indicated that each of these site-directed mutants primarily retained their activity and had high structural similarity of their protein fold. A computed structure model of T. cruzi hexokinase (TcHxK), which was produced by the artificial intelligence system AlphaFold, was compared to an X-ray crystal structure of TcGlcK. Our structural analysis revealed that TcHxK lacked an F337 counterpart residue and probably exists in the monomeric form. We proposed that the d-glucosamine analogue inhibitors that are structurally similar to CBZ-GlcN may not bind as strongly in TcHxK as they do in TcGlcK because of absent van der Waals contact from residue side chains.

High-intensity pulsed electric field-assisted acidic extraction of pectin from citrus peel: Physicochemical characteristics and emulsifying properties

Sustainable innovation seeks more energy-efficient processes for producing highly demanded products from industrial by-products. This study follows this endeavor. Comparisons were made on two processes for producing pectins from citrus peel as well as the two derived pectin products: a high-intensity pulsed electric field (HIPEF) pretreatment of citrus peel powder followed by a milder acidic extraction (pH 2, heating at 70 °C for 1 h; pectin termed HIPEF-CP), and a conventional direct hot-acid extraction (pH 2, heating at 90 °C for 2 h; pectin termed CP). HIPEF-assisted extraction significantly improved pectin yield (by 8.48%) and production efficiency (by 100.23%) while reducing energy consumption. Both were low-methoxyl pectins with similar branching degrees and contents of rhamnogalacturonan-I (RG-I), protein, phenolic compounds, total alkaloids and vitamin C. Compared with CP, HIPEF-CP contained higher homogalacturonan content, higher galactose content, higher galacturonic acid content, lower arabinose content, lower xylose content, slightly lower degree of methyl esterification, higher linearity, lower side chain size, higher molecular weight, and wider molecular weight distribution. The antioxidant, emulsifying and emulsion-stabilizing abilities of HIPEF-CP were superior to those of CP, though both pectins were satisfactory emulsifiers, exhibiting good antioxidant activities and emulsifying capacities at pectin concentrations not lower than 1.0%. The HIPEF pretreatment of citrus peel made the subsequent acidic pectin extraction feasible under milder conditions, to produce pectin with desired antioxidant and emulsifying capacities.

High-Performance n-Type Organic Thermoelectrics Enabled by Synergistically Achieving High Electron Mobility and Doping Efficiency.

n-Doped polymers with high electrical conductivity (σ) are still very scarce in organic thermoelectrics (OTEs), which limits the development of efficient organic thermoelectric generators. A series of fused bithiophene imide dimer-based polymers, PO8, PO12, and PO16, incorporating distinct oligo(ethylene glycol) side-chain to optimize σ is reported here. Three polymers show a monotonic electron mobility decrease as side-chain size increasing due to the gradually lowered film crystallinity and change of backbone orientation. Interestingly, polymer PO12 with a moderate side-chain size delivers a champion σ up to 92.0 S cm-1 and a power factor (PF) as high as 94.3 µW m-1 K-2 in the series when applied in OTE devices. The PF value is among the highest ones for the solution-processing n-doped polymers. In-depth morphology studies unravel that the moderate crystallinity and the formation of 3D conduction channel derived from bimodal orientation synergistically contribute to high doping efficiency and large charge carrier mobility, thus resulting in high performance for the PO12-based OTEs. The results demonstrate the great power of simple tuning of side chain in developing n-type polymers with substantial σ for improving organic thermoelectric performance.

Identification of the glycosylphosphatidylinositol-specific phospholipase A2 (GPI-PLA2) that mediates GPI fatty acid remodeling in Trypanosoma brucei

The biosynthesis of glycosylphosphatidylinositol (GPI)-anchored proteins (GPI-APs) in the parasitic protozoan Trypanosoma brucei involves fatty acid remodeling of the GPI precursor molecules before they are transferred to protein in the endoplasmic reticulum. The genes encoding the requisite phospholipase A2 and A1 activities for this remodeling have thus far been elusive. Here, we identify a gene, Tb927.7.6110, that encodes a protein that is both necessary and sufficient for GPI-phospholipase A2 (GPI-PLA2) activity in the procyclic form of the parasite. The predicted protein product belongs to the alkaline ceramidase, PAQR receptor, Per1, SID-1, and TMEM8 (CREST) superfamily of transmembrane hydrolase proteins and shows sequence similarity to Post-GPI-Attachment to Protein 6 (PGAP6), a GPI-PLA2 that acts after transfer of GPI precursors to protein in mammalian cells. We show the trypanosome Tb927.7.6110 GPI-PLA2 gene resides in a locus with two closely related genes Tb927.7.6150 and Tb927.7.6170, one of which (Tb927.7.6150) most likely encodes a catalytically inactive protein. The absence of GPI-PLA2 in the null mutant procyclic cells not only affected fatty acid remodeling but also reduced GPI anchor sidechain size on mature GPI-anchored procyclin glycoproteins. This reduction in GPI anchor sidechain size was reversed upon the re-addition of Tb927.7.6110 and of Tb927.7.6170, despite the latter not encoding GPI precursor GPI-PLA2 activity. Taken together, we conclude that Tb927.7.6110 encodes the GPI-PLA2 of GPI precursor fatty acid remodeling and that more work is required to assess the roles and essentiality of Tb927.7.6170 and the presumably enzymatically inactive Tb927.7.6150.

Impact of side-chain engineering on quantum efficiency and voltage losses in organic solar cells

Increasing the size of the side chains of the donor or the acceptor materials is a highly effective strategy to reduce voltage losses, and increase the open-circuit voltage (Voc) of organic solar cells (OSCs). However, higher Voc does not necessarily translate to improved overall performance. To optimize side-chains and improve the performance of OSCs, the origin of the impact of the increased size of the donor and/or acceptor side side-chains size on the performance of OSCs is investigated. The study demonstrates that increasing the size of donor side chains can increase Voc, but it can also lead to deteriorated molecular packing, limiting overall solar cell performance. On the other hand, increasing the size of acceptor side chains can also increase Voc and improve molecular packing properties of the active layer, resulting in improved solar cell performance. Finally, the study shows that the best photovoltaic performance is achieved when both the donor and acceptor have large side chains. This research establishes the relationship between side chains of active materials, molecular packing properties, and the energetics of the donor/acceptor active layer, which is crucial for overcoming performance bottlenecks in OSCs.

Designing Fluorescent Covalent Organic Frameworks by Controlling Layer Spacing, Size of Aromatic Linker and Side Chains for Detection of Nitrofurazone

AbstractA new imine‐linked covalent organic framework (COFDHA‐TAPB) with strong fluorescence is designed by using 2,5‐dihydroxybenzaldehyde (DHA) and 1,3,5‐tri(4‐aminophenyl)benzene (TAPB) as monomers. The TAPB has a suitable aromatic skeleton in which slight distortion between phenyl groups reduces aggregation‐caused quenching (ACQ). The hydroxyl group side chains of DHA form hydrogen bond with the imine bonds of COFDHA‐TAPB to restrict intramolecular rotations. Hydrogen bonds are also formed between different layers of COFDHA‐TAPB, which further restricts supramolecular rotation by narrowing the layer spacing. Moreover, the COFDHA‐TAPB exhibits a hollow sphere structure, which also reduces ACQ and intramolecular rotation. Therefore, COFDHA‐TAPB has a strong emission peak at 408 nm, which is used for nitrofurazone detection. The detection linear range is 0.33 µm–0.197 mm (0.066–39 µg mL−1), and the detection limit is 0.11 µm (0.022 µg mL−1). This work also provides an important guideline to design strongly fluorescent covalent organic framework by controlling layer spacing, aromatic linkers sizes and side chains of monomers for sensors.

Synergetic Effects of Alanine and Glycine in Blob-Based Methods for Predicting Protein Folding Times.

The polypeptide PGlyAlaGlu was prepared with 20 mol % glycine (Gly), 36 mol % d,l-alanine (Ala), and 44 mol % d,l-glutamic acid (Glu) and labeled with the dye 1-pyrenemethylamine to yield a series of Py-PGlyAlaGlu samples. The fluorescence decays of the Py-PGlyAlaGlu samples were analyzed according to the fluorescence blob model (FBM) to obtain the number Nblobexp of amino acids (aa's) encompassed inside the subvolume Vblob of the polypeptide probed by an excited pyrene. An Nblobexp value of 29 (±2) was retrieved for Py-PGlyAlaGlu, which was much larger than for any of the copolypeptide PGlyGlu or PAlaGlu prepared with either Gly and Glu or Ala and Glu, respectively. The continuous increase in Nblobexp with decreasing side chain size (SCS) from 10 aa's for PGlu to 16 aa's for PAlaGlu and 22 aa's for PGlyGlu was used earlier to define the reach of an aa and determine the groups of aa's that could interact with each other along a polypeptide backbone according to their SCS. These groups of aa's, referred to as blobs, led to the implementation of blob-based models (BBM) to predict the folding time τFtheo,BBM of 145 proteins, which was found to match their experimental folding time τFexp with a relatively high 0.71 correlation coefficient. Nevertheless, the much higher Nblobexp value found for Py-PGlyAlaGlu compared to all other pyrene-labeled polypeptides studied to date indicates that the reach of aa's along a polypeptide sequence is affected not only by SCS but also by synergetic effects between different aa's. Following this new insight, a revised BBM was implemented to predict τFtheo,BBM for 195 proteins assuming the existence or absence of synergies to control the interactions between aa's along a polypeptide sequence. Similarly good correlation coefficients of 0.71 and 0.74 were obtained for a direct 1:1 comparison of τFexp and τFtheo,BBM for the 195 proteins without and with synergies, respectively. This result suggests that synergetic effects between different aa's have little effect on τFtheo,BBM predicted from BBM underlying the robustness of this methodology.

Chemically Acylated tRNAs are Functional in Zebrafish Embryos.

Genetic code expansion has pushed protein chemistry past the canonical 22 amino acids. The key enzymes that make this possible are engineered aminoacyl tRNA synthetases. However, as the number of genetically encoded amino acids has increased over the years, obvious limits in the type and size of novel side chains that can be accommodated by the synthetase enzyme become apparent. Here, we show that chemically acylating tRNAs allow for robust, site-specific incorporation of unnatural amino acids into proteins in zebrafish embryos, an important model organism for human health and development. We apply this approach to incorporate a unique photocaged histidine analogue for which synthetase engineering efforts have failed. Additionally, we demonstrate optical control over different enzymes in live embryos by installing photocaged histidine into their active sites.

A comparison study on polysaccharides extracted from Rosa sterilis S.D.Shi using different methods: Structural and in vitro fermentation characterizations

In this study, the structural and in vitro fermentation characterizations of Rosa sterilis S.D.Shi polysaccharides (RSP), extracted by hot water (HW), acid (AA), alkali (AK) and enzyme (EM) were investigated for the first time. The results indicated that extraction methods exhibited significant effects on the structure of RSPs, thus resulting in different probiotic effects. HW-RSP and AA-RSP had high contents of Gal, Glc and GalA, while AK-RSP and EM-RSP mainly contained Ara, Gal and GalA. EM-RSP was rich in RG-I and its size of average side chain were the largest. Moreover, HW-RSP and AK-RSP exhibited the smallest (57.55 kDa) and largest (922.20 kDa) molecular weights, respectively. All RSPs promoted the production of total SCFAs and the growth of beneficial bacteria like Bifidobacterium, Bacteroides, Faecalibacterium and Paraclostrium to varying degrees, but inhibited the growth of pathogenic bacteria such as Escherichia-shigella, thereby regulating the composition of gut microbiota. Furthermore, the function prediction results showed that EM-RSP had the most special metabolic pathways. Collectively, our findings provide new insights into the relationship between the structure and probiotic function of RSPs, and offer theoretical basis for the development of functional products of Rosa sterilis S.D.Shi.

Effect of the N-Alkyl Side Chain on the Amide-Water Interactions.

Amide-water interactions influence the structure and functions of amide-based systems, such as proteins and homopolymers. In particular, the N-alkylation of the amide unit appears to play a critical role in defining the interactions of the amide group. Previous studies have linked the thermal behavior of amide-based polymers to the nature of their N-alkyl side chain. However, the connection between the chemical structure of the N-alkyl and the hydration of the amide remains elusive. In this study, the solvation structure and dynamics of amides, having differing N-alkyl groups, are investigated using a combination of linear and nonlinear infrared spectroscopies and computational methods. Interestingly, the dynamics of the amide local environment do not slow down as the N-alkyl side chain becomes bulkier, but rather speeds up. Computational calculations confirm the hydration dynamics and assign the effect to smaller amplitude and faster rotations of the bulkier group. It is also observed experimentally that the hydrogen-bond making and breaking between water and the amide carbonyl do not directly relate to the size of the N-alkyl side chain. The bulkier N-isopropyl substituent presents significantly slower chemical exchange dynamics than smaller chains (ethyl and methyl), but the two small groups do not present a major difference. The hydrogen-bond making and breaking disparities and similarities among groups are well modeled by the theory demonstrating that the N-alkyl group affects the amide hydration structure and dynamics via a steric effect. In summary, the results presented here show that the size of the N-substituted alkyl group significantly influences the hydration dynamics of amides and stress the importance of considering this effect on much larger systems, such as polymers.

Folding Coarse-Grained Oligomer Models with PyRosetta.

Non-biological foldamers are a promising class of macromolecules that share similarities to classical biopolymers such as proteins and nucleic acids. Currently, designing novel foldamers is a non-trivial process, often involving many iterations of trial synthesis and characterization until folded structures are observed. In this work, we aim to tackle these foldamer design challenges using computational modeling techniques. We developed CG PyRosetta, an extension to the popular protein folding python package, PyRosetta, which introduces coarse-grained (CG) residues into PyRosetta, enabling the folding of toy CG foldamer models. Although these models are simplified, they can help explore overarching physical hypotheses about how oligomers can form. Through systematic variation of CG parameters in these models, we can investigate various folding hypotheses at the CG scale to inform the design process of new foldamer chemistries. In this study, we demonstrate CG PyRosetta's ability to identify minimum energy structures with a diverse structural search over a range of simple models, as well as two hypothesis-driven parameter scans investigating the effects of side-chain size and internal backbone angle on secondary structures. We are able to identify several types of secondary structures from single- and double-helices to sheet-like and knot-like structures. We show how side-chain size and backbone bond angle both play an important role in the structure and energetics of these toy models. Optimal side-chain sizes promote favorable packing of side chains, while specific backbone bond angles influence the specific helix type found in folded structures.