Conformational Distribution Research Articles

Potential energy surfaces of the [formula omitted] clusters in solution phase

In the present work, we have studied the effects of the implicit solvent on the structural and energetic parameters of Cu2+(MeOH)n=1-8 clusters. Initially, we explored the potential energy surfaces (PESs) obtained in the solution phase using the functional DFT M06-2X method, in conjunction with the 6–31++G** Pople basis set, and compared them with isomers of the same complexes optimized in the gaseous phase. The implicit solvent is described here by the polarized continuum model of integral equation formalism (IEF-PCM). Subsequently, we reported the temperature dependence and the binding electronic energies per methanol molecule. Our investigations reveal that the 6- and 5-coordinate isomers occupy the ground states on the PESs of the Cu2+(MeOH)n=1-8 clusters. The stability rules of the Cu2+ ion established in the gas phase are best adhered to in the implicit solvent. Regarding the temperature dependence of the solution phase conformer distribution, symmetric and compact structures, as well as those with a high coordination number (CN), dominate the population of the Cu2+(MeOH)n=1-8 clusters at all temperatures. Notably, the populations of clusters with sizes n=7-8 are exclusively dominated by hexa-coordinated structures at all temperatures, while penta- and tetra-coordinated isomers are disadvantaged. For the determination of the binding electronic energy, using a function fit, we computed these energies to be -1589kJ mol−1 in the implicit solvent and -7150kJ mol−1 in the gaseous phase. This significant difference is attributable to the interactions between the methanol molecules and the implicit solvent, which are present in the solvent phase but absent in a gaseous medium. This difference is further supported by the analysis of the Wiberg bond index of the metal–ligand interactions of the clusters in the two media.

Kinetic Resolution of the Atomic 3D Structures Formed by Ground and Excited Conformational States in an RNA Dynamic Ensemble.

Knowing the 3D structures formed by the various conformations populating the RNA free-energy landscape, their relative abundance, and kinetic interconversion rates is required to obtain a quantitative and predictive understanding of how RNAs fold and function at the atomic level. While methods integrating ensemble-averaged experimental data with computational modeling are helping define the most abundant conformations in RNA ensembles, elucidating their kinetic rates of interconversion and determining the 3D structures of sparsely populated short-lived RNA excited conformational states (ESs) remains challenging. Here, we developed an approach integrating Rosetta-FARFAR RNA structure prediction with NMR residual dipolar couplings and relaxation dispersion that simultaneously determines the 3D structures formed by the ground-state (GS) and ES subensembles, their relative abundance, and kinetic rates of interconversion. The approach is demonstrated on HIV-1 TAR, whose six-nucleotide apical loop was previously shown to form a sparsely populated (∼13%) short-lived (lifetime ∼ 45 μs) ES. In the GS, the apical loop forms a broad distribution of open conformations interconverting on the pico-to-nanosecond time scale. Most residues are unpaired and preorganized to bind the Tat-superelongation protein complex. The apical loop zips up in the ES, forming a narrow distribution of closed conformations, which sequester critical residues required for protein recognition. Our work introduces an approach for determining the 3D ensemble models formed by sparsely populated RNA conformational states, provides a rare atomic view of an RNA ES, and kinetically resolves the atomic 3D structures of RNA conformational substates, interchanging on time scales spanning 6 orders of magnitude, from picoseconds to microseconds.

Effect of magnetic field modification on oxidative stability of myoglobin in sarcoplasm systems

This study aimed to investigate the effect of magnetic fields (0, 3, 6, 12 mT) on the oxidation characteristics of myoglobin (Mb) in the sarcoplasmic protein (SP) system and to understander the underlying mechanism. The metmyoglobin content, Soret band of heme iron porphyrin, protein conformation and molecular weight distribution were measured in different Mb and SP samples. The results showed that the primary oxidation site of hydroxyl radical on Mb was likely to be the porphyrin ring structure and the side chain group of protein rather than the central iron atoms, what’s more, 12 mT magnetic field treatment had an inhibitory effect on the oxidative damage induced by hydroxyl radical.

Comparative Analysis of Conformational Dynamics and Systematic Characterization of Cryptic Pockets in the SARS-CoV-2 Omicron BA.2, BA.2.75 and XBB.1 Spike Complexes with the ACE2 Host Receptor: Confluence of Binding and Structural Plasticity in Mediating Networks of Conserved Allosteric Sites.

In the current study, we explore coarse-grained simulations and atomistic molecular dynamics together with binding energetics scanning and cryptic pocket detection in a comparative examination of conformational landscapes and systematic characterization of allosteric binding sites in the SARS-CoV-2 Omicron BA.2, BA.2.75 and XBB.1 spike full-length trimer complexes with the host receptor ACE2. Microsecond simulations, Markov state models and mutational scanning of binding energies of the SARS-CoV-2 BA.2 and BA.2.75 receptor binding domain complexes revealed the increased thermodynamic stabilization of the BA.2.75 variant and significant dynamic differences between these Omicron variants. Molecular simulations of the SARS-CoV-2 Omicron spike full-length trimer complexes with the ACE2 receptor complemented atomistic studies and enabled an in-depth analysis of mutational and binding effects on conformational dynamic and functional adaptability of the Omicron variants. Despite considerable structural similarities, Omicron variants BA.2, BA.2.75 and XBB.1 can induce unique conformational dynamic signatures and specific distributions of the conformational states. Using conformational ensembles of the SARS-CoV-2 Omicron spike trimer complexes with ACE2, we conducted a comprehensive cryptic pocket screening to examine the role of Omicron mutations and ACE2 binding on the distribution and functional mechanisms of the emerging allosteric binding sites. This analysis captured all experimentally known allosteric sites and discovered networks of inter-connected and functionally relevant allosteric sites that are governed by variant-sensitive conformational adaptability of the SARS-CoV-2 spike structures. The results detailed how ACE2 binding and Omicron mutations in the BA.2, BA.2.75 and XBB.1 spike complexes modulate the distribution of conserved and druggable allosteric pockets harboring functionally important regions. The results are significant for understanding the functional roles of druggable cryptic pockets that can be used for allostery-mediated therapeutic intervention targeting conformational states of the Omicron variants.

Dimethylpiperazine on Air-Water Interface: Vibrational Sum frequency Generation study of a cyclic tertiary amine

Dimethyl piperazine (DMP) is a weakly basic, cyclic, tertiary diamine. Being a saturated 6-membered ring, it may attain a number of energetically close conformational orientations in the ground state. In a particular environment, its conformational distribution depends on the stabilising factors present in the surroundings. Though soluble in water, it is expected to have substantial surface propensity due to presence of multiple –CH2 and –CH3 bonds. Detection of Bohlmann bands in the C–H stretch region of the Vibrational Sum Frequency Generation (VSFG) spectrum revealed that comparatively higher energy chair conformer with one axial and one equatorial –CH3 bond is present on the pure liquid DMP-air interface. At the air-aqueous solution interface, those bands were found to disappear as the lone electron pair on N-atom is engaged in hydrogen bonding with water molecule. Due to this hydrogen bonding, the peak of “dangling free OH” bonds disappeared from VSFG spectrum of water molecules at air–water interface. Alongwith this hydrogen bonding, the hydrophobic nature of the –CH3 bonds of DMP molecules cause disorganisation of native hydrogen bonded network of water molecules in the air–water interface. Structure and orientation of DMP is expected to be pH-responsive since the chemical conditions of the surrounding medium directly affect the extent of protonation of the amine group. Upon addition of HCl to the bulk, protonated DMP ions, too, could be detected on the air-solution interface by their VSFG spectrum which were considerably different from unprotonated DMP. As the bulk pH of solution changed towards more acidic, spectral features of VSFG spectra of DMP on the surface showed significant change, implying variation in the surface pH, as structure and orientation changes at different degrees of protonation. Since the VSFG spectral features of DMP was found to be pH-responsive, it can be utilised to ascertain the pH of any surface that has DMP absorbed on it. pH-sensitivity of the DMP molecules on air–water interface also suggest that orientation of headgroups will have some effect on the surface orientation of cationic surfactants with amine based headgroups.

Direction Modulated Brachytherapy Tandem Model Applicators for Treatment Planning of Multi-Institutional Cervical Cancer Cases

Direction Modulated Brachytherapy (DMBT) offers a means of utilizing an anisotropic source to create more conformal dose distributions when integrated with image-guided adaptive brachytherapy (IGABT). Authors sought to validate the implementation of nine unique six-channeled, MRI-compatible, novel DMBT tandem applicators of varying physical dimensions within Varian's BrachyVision® (v16.1) treatment planning system (BV-TPS). A total of 110 retrospective clinically delivered high-dose-rate (HDR) cervical cancer brachytherapy plans, from three institutions, were re-planned for each of the nine DMBT tandem models within the BV-TPS, using the latest VEGO® inverse optimization algorithm, with dose heterogeneity accounted for through AcurosBV®. Plans consisted of both intracavitary (77 plans) and interstitial (33 plans) cases with an average prescription dose and high-risk clinical target volumes (CTVHR) of 607±113 cGy and 26.96±14.95 [range 6.70-69.58] cm3, respectively. During re-planning, the conventional tandems were replaced by one of the nine DMBT tandem models while leaving ovoids or rings, and needles (if present), in place. A two-step inverse optimization process was performed such that the lowest possible organs at risk (OAR) D2cc doses could be achieved while 1) keeping equivalent target coverage (ΔCTVHR-D90 to within ±0.5%) and, at the same time, 2) maintaining the general pear-shape dose distribution of the original plans. Noteworthy improvements in plan quality were achieved by all nine DMBT tandem models, which are presented in Table 1. Irrespective of the model, about ∼50 cGy reduction in D2cc across all OARs appear feasible. There is also a general trend of D2cc reductions' magnitude becoming smaller as the CTVHR volume increased due to loss in modulation at distance. Additionally, D2cc reductions in terms of EQD2 [Gy] were calculated assuming each re-plan was delivered throughout the course of treatment, which includes the external beam radiotherapy dose of 45 Gy and showed significant reductions of -6.29±4.38 Gy, -3.80±2.06 Gy, and -4.86±3.02 Gy for the bladder, rectum, and sigmoid, respectively, for DMBT model #9 for example. We have successfully incorporated nine DMBT tandem models into a commercial TPS and re-planned 110 cases, to a total of 990 plans. All nine DMBT tandem models were each able to generate notable D2cc reductions to OARs (∼50 cGy), without compromising target coverage, across plans from multiple institutions with various clinical/optimization practices. The results indicate both a promising impact and smooth integration of DMBT tandem technology into modern clinical IGABT workflow.

Prospective Dosimetric Comparison Study Between Volumetric Modulated Arc Therapy and Intracavitary Brachytherapy for Cervical Cancer

Although volumetric modulated arc therapy (VMAT) boost can achieve highly conformal dose distributions for cervical cancer, VMAT has the disadvantage of requiring set-up and organ motion margins. This study prospectively recruited patients with the cervical cancer and compared VMAT plan with intracavitary brachytherapy (ICBT) plan. All patients treated with ICBT for locally advanced cervical cancer between April 2020 and September 2022 were enrolled. Patients had whole-pelvis radiotherapy, followed by CT scans with and without the tandem and ovoid in the same session (for the planning of ICBT and VMAT, respectively). ICBT planning characterizes the high-risk clinical target volume (HR-CTV) as the target volume and the bladder, rectum, sigmoid colon and small bowel loop as the organ at risk (OAR). VMAT planning defines the HR-CTV + 3 mm as the target volume and bladder, rectum + 3 mm (planning organ at risk volume (PRV) rectum), sigmoid colon + 3 mm (PRV sigmoid) and bowel bag as the OAR to account for set-up and organ motion. ICBT and VMAT plans were optimized for maximal dose received by at least 90% (D90%) of the target volume without impairing the dose constraints for the OARs. The prescribed dose (PD) was 26 Gy in 4 fractions. The dose constraints were determined as 25.2 Gy for D2 ml in the bladder and 20 Gy for D2 ml in the other OARs. The D90% and D100% of the target volume and D2 ml of OARs were compared between 2 plans using paired two-tailed Student's t test. Seventeen patients were enrolled. Dose and volume parameters for the 2 plans are shown in Table 1. Of the 17 patients, D90% of the target volume received 100% PD in 4 cases with ICBT plans, in 6 cases for VMAT plans, and in 2 cases with both methods. For D90% of the target volume, ICBT plans were greater than VMAT plans in 4 cases, with a maximum difference of 5.6 Gy (ICBT: 26.0 Gy, SBRT: 20.4 Gy). VMAT plans were higher than ICBT plans in 11 cases, with a maximum difference of 10.3 Gy (ICBT: 14.5 Gy, SBRT: 24.8 Gy). The dose-limiting OARs to attain D90% of target volume were bladder in 12 cases and small bowel loop in 1 case for ICBT plans, while PRV rectum in 11 cases, PRV sigmoid in 4 cases and bowel bag in 1 case for VMAT plans. This prospective study with 17 ICBT-eligible patients revealed D90% of the target volume demonstrated no substantial difference between VMAT and ICBT plans, while D100% showed a significant increase in VMAT plan compared to ICBT plan. Even with a set-up and organ motion margins on the HR-CTV and OARs, VMAT may have a dosimetric advantage over ICBT if the target geometry is complicated and close to the OARs.

DFT-Based Calculation of Molecular Hyperpolarizability and SFG Intensity of Symmetric and Asymmetric Stretch Modes of Alkyl Groups.

Vibrational sum frequency generation (SFG) spectroscopy has been extensively used for obtaining structural information of molecular functional groups at two-dimensional (2D) interfaces buried in the gas or liquid medium. Although the SFG experiment can be done elegantly, interpreting the measured intensity in terms of molecular orientation with respect to the lab coordinate is quite complicated. One of the main reasons is the difficulty of determining the hyperpolarizability tensors of even simple molecules that govern their SFG responses. The single-bond polarizability derivative model has been proposed to estimate the relative magnitude of SFG-active hyperpolarizability by assuming that the perturbation associated to each vibration is negligible. In this study, density functional theory was used to calculate the polarizability and dipole derivative tensors of the CH3 stretch mode of CH3I, CH3CH2I, CH3OH, and CH3CH2OH. Then, the hyperpolarizability tensors of symmetric and asymmetric vibration modes were calculated considering the Boltzmann distribution of representative conformers, which allowed us to theoretically calculate their SFG intensities at all polarization combinations as a function of the tilt angle of the CH3 group with respect to the surface normal direction. Then, the ratios of the calculated SFG intensities for the CH3 symmetric and asymmetric stretch peaks used in experimental studies for the CH3 tilt angle determination were compared. This comparison clearly showed that the effect of vibrational coupling among neighboring functional groups is significant and cannot be assumed to be negligible. This study presents new parameters that can be used in determining the average tilt angle of the CH3 group at the 2D interface with SFG measurements as well as limitations of the method.

Types and Genesis of Siderite in the Coal-Bearing Beds of the Late Permian Xuanwei Formation in Eastern Yunnan, China

The Late Permian strata of the Xuanwei Formation in the eastern Yunnan region exhibit extensive diverse morphological features within siderite deposits. These variations in siderite deposits suggest potential differences in their formation processes. In this study, fieldwork and comprehensive indoor studies revealed four distinct forms of siderite deposits: stratiform-laminated, lens-like nodule, sandstone cementation, and fracture filling. The stratiform-laminated siderite, varying in color from bluish-grey to dark grey, is composed of uniformly sized microcrystalline to fine-grained siderite along with detrital matter, displaying precise layering and banding structures that suggest direct deposition from cyclic iron-rich seawater under reducing conditions. Lens-like-nodule siderite, which appears grey-yellow, is composed of mud microcrystalline siderite, medium to coarse-grained pseudo-ooids, and glauconite. It shows conformable distribution characteristics resulting from the diagenetic differentiation of iron-rich sediments under reducing conditions during the diagenetic and early diagenetic periods. Siderite as sandstone cementation exhibits a yellow-brown color and consists of dispersed colloidal siderite and cemented siderite clumps that fill intergranular pores of detrital particles. It precipitated under reducing conditions within those intergranular pores. Siderite filling fractures typically appear as vein-like or network-like structures intersecting bedding at large angles. They exhibit grain structures with significant variations in size. These siderite deposits exhibit exceptional purity and result from siderite dissolution during sedimentary periods, followed by reprecipitation within regional extensional fractures during the diagenetic phase. The primary occurrence of siderite deposits in the study area is within coal-bearing strata, as revealed by the integration of sedimentary profiles and sedimentary facies analysis. The coal-bearing strata, influenced by the Emeishan large igneous province, underwent iron enrichment during and after volcanic eruptions while developing a reducing environment, which was facilitated by abundant vegetation. Consequently, geological processes led to siderite layers, lens-like siderite nodules, and siderite cementation. The Yanshan orogeny induced extensive high-angle fracture development in epigenetic coal-bearing strata, facilitating fluid circulation and the redistribution of soluble siderite. This geological activity resulted in the formation of vein-like structures composed of siderite.

Development and Quality Assurance of Multileaf Collimator (MLC) Auto-Feathering Junctions for Multi-Isocenter Supine Volumetric Modulated Arc Therapy (VMAT) Craniospinal Axis Irradiation on Halcyon.

Currently, there is alack of methods and tools that efficiently evaluate the auto-feathering junctions created by multileaf collimator (MLCs) for supine volumetric modulated arc therapy (VMAT) craniospinalirradiation (CSI) plans. We have investigated the feasibility of stitching together multi-isocenter fluence maps to then analyze the feathered junctions for patient-specific quality assurance (QA). Furthermore, we investigated the capability of Halcyon for the treatment of CSI patients.Three patients, who previously underwent VMAT CSI treatment on TrueBeam (6-MV flattening filter-free (FFF)) for 36 Gy in 20 fractionswerereplanned for Halcyon. A multi-isocenter approach with only translational superior-inferior shifts was used for both platforms. Each isocenter consists of two full arcs with anterior avoidance sectors, ±5° collimator rotations between arcs, and 5-8 cm of overlapping MLC auto-feathering junctions. All plans were QA'd via electronicportalimaging device (EPID) portal dosimetry and analyzed with a gamma criteria of 3%/3 mm. A variety of plan quality metrics were analyzed to evaluate dose distributions to the target, doses to organs at risk (OARs), and integral dose to the patient. A MATLAB script was developed to stitch the calculated and measured fluence maps in order to perform patient-specific QA for the composite fluence.The Halcyon plans provided highly conformal and homogenous dose distributions to the entire CSI target, superior to the clinical TrueBeam plans, while sparing critical organs with significantly lower values of V10Gy and V18Gy by up to 2% and 2.5%, respectively.Qualitative depictions of vertical dose profiles from the stitched DICOM of the entire CSI target for both planned and delivered fluence maps demonstrated equivalency, with slightly lower average pass rates with Halcyon (97%) compared to TrueBeam(99.9%). This approach to stitch multiple measured versus calculated EPID fluence maps has shown to be a feasible and accurate method and will be helpful for comprehensive VMAT CSI QA on both platforms. Further implementation of this script will be used in examining dosimetric impacts of daily patient positioning errors at MLC auto-feathering junctions.

Pencil Beam Scanning Bragg Peak FLASH Technique for Ultra-High Dose Rate Intensity-Modulated Proton Therapy in Early-Stage Breast Cancer Treatment.

Bragg peak FLASH-RT can deliver highly conformal treatment and potentially offer improved normal tissue protection for radiotherapy patients. This study focused on developing ultra-high dose rate (≥40 Gy × RBE/s) intensity-modulated proton therapy (IMPT) for hypofractionated treatment of early-stage breast cancer. A novel tracking technique was developed to enable pencil beaming scanning (PBS) of single-energy protons to adapt the Bragg peak (BP) to the target distally. Standard-of-care PBS treatment plans of consecutively treated early-stage breast cancer patients using multiple energy layers were reoptimized using this technique, and dose metrics were compared between single-energy layer BP FLASH and conventional IMPT plans. FLASH dose rate coverage by volume (V40Gy/s) was also evaluated for the FLASH sparing effect. Distal tracking can precisely stop BP at the target distal edge. All plans (n = 10) achieved conformal IMPT-like dose distributions under clinical machine parameters. No statistically significant differences were observed in any dose metrics for heart, ipsilateral lung, most ipsilateral breast, and CTV metrics (p > 0.05 for all). Conventional plans yielded slightly superior target and skin dose uniformities with 4.5% and 12.9% lower dose maxes, respectively. FLASH-RT plans reached 46.7% and 61.9% average-dose rate FLASH coverage for tissues receiving more than 1 and 5 Gy plan dose total under the 250 minimum MU condition. Bragg peak FLASH-RT techniques achieved comparable plan quality to conventional IMPT while reaching adequate dose rate ratios, demonstrating the feasibility of early-stage breast cancer clinical applications.

Accelerating the characterization of dynamic DNA origami devices with deep neural networks

Mechanical characterization of dynamic DNA nanodevices is essential to facilitate their use in applications like molecular diagnostics, force sensing, and nanorobotics that rely on device reconfiguration and interactions with other materials. A common approach to evaluate the mechanical properties of dynamic DNA nanodevices is by quantifying conformational distributions, where the magnitude of fluctuations correlates to the stiffness. This is generally carried out through manual measurement from experimental images, which is a tedious process and a critical bottleneck in the characterization pipeline. While many tools support the analysis of static molecular structures, there is a need for tools to facilitate the rapid characterization of dynamic DNA devices that undergo large conformational fluctuations. Here, we develop a data processing pipeline based on Deep Neural Networks (DNNs) to address this problem. The YOLOv5 and Resnet50 network architecture were used for the two key subtasks: particle detection and pose (i.e. conformation) estimation. We demonstrate effective network performance (F1 score 0.85 in particle detection) and good agreement with experimental distributions with limited user input and small training sets (~ 5 to 10 images). We also demonstrate this pipeline can be applied to multiple nanodevices, providing a robust approach for the rapid characterization of dynamic DNA devices.

Zinc Ions Modulate YY1 Activity: Relevance in Carcinogenesis.

YY1 is widely recognized as an intrinsically disordered transcription factor that plays a role in development of many cancers. In most cases, its overexpression is correlated with tumor progression and unfavorable patient outcomes. Our latest research focusing on the role of zinc ions in modulating YY1's interaction with DNA demonstrated that zinc enhances the protein's multimeric state and affinity to its operator. In light of these findings, changes in protein concentration appear to be just one element relevant to modulating YY1-dependent processes. Thus, alterations in zinc ion concentration can directly and specifically impact the regulation of gene expression by YY1, in line with reports indicating a correlation between zinc ion levels and advancement of certain tumors. This review concentrates on other potential consequences of YY1 interaction with zinc ions that may act by altering charge distribution, conformational state distribution, or oligomerization to influence its interactions with molecular partners that can disrupt gene expression patterns.

Conformational Manifold Sampled by Two Short Linear Motif Segments Probed by Circular Dichroism, Vibrational, and Nuclear Magnetic Resonance Spectroscopy.

Disordered protein segments called short linear motifs (SLiM) serve as recognition sites for a variety of biological processes and act as targeting signals, modification, and ligand binding sites. While SLiMs do not adopt one of the known regular secondary structures, the conformational distribution might still reflect the structural propensities of their amino acid residues and possible interactions between them. In the past, conformational analyses of short peptides provided compelling evidence for the notion that individual residues are less conformationally flexible than locally expected for a random coil. Here, we combined various spectroscopies (NMR, IR, vibrational, and UV circular dichroism) to determine the Ramachandran plots of two SLiM motifs, i.e., GRRDSG and GRRTSG. They are two representatives of RxxS motifs that are capable of being phosphorylated by protein kinase A, an enzyme that plays a fundamental role in a variety of biological processes. Our results reveal that the nearest and non-nearest interactions between residues cause redistributions between polyproline II and β-strand basins while concomitantly stabilizing extended relative to turn-forming and helical structures. They also cause shifts in basin positions. With increasing temperature, β-strand populations become more populated at the expense of polyproline II. While molecular dynamics simulations with Amber ff14SB and CHARMM 36m force fields indicate residue-residue interactions, they do not account for the observed structural changes.

Quantum dynamics of the internal motion of biphenyl-based molecular junctions.

Single molecule junctions based on selected 4,4'-biphenyldithiol and 4,4'-dicyanobiphenyl derivatives bonded to gold electrodes are analyzed from a dynamical point of view. A fully quantum mechanical description of the internal rotation of the biphenyl moiety is carried out in terms of the nuclear wavepacket dynamics obtained by the solution of the time-dependent Schrödinger equation expressed in terms of the torsion angle between the phenyl rings. The required potential energy surfaces are computed using abinitio electronic structure methods. The nature and positions of the substituents on the phenyl rings determine the features of the potential energy surfaces. The effect of the initial conditions on the time propagation of the nuclear wavepackets and, as a consequence, on the evolution of the conformational distribution is also analyzed. In addition, the conductances at zero bias for the nanojunctions were computed for different conformations of the biphenyl fragments. Weighted by the wavepacket amplitudes, non-stationary conductance expectation values, and time-averaged torsion angles and conductances for the entire simulation are obtained. The consequences of using the time-averaged values to perform a linear regression between the conductance and the square of the cosine of the dihedral angle between the phenyl rings are analyzed and compared to the usual static approach based only on the information for equilibrium geometries. The study of the time dependent conformational variations of the biphenyl moieties in the nanojunctions allows for a better understanding of the quantum chemical phenomena that affect their transport properties.

Atomic-scale insight into molecular adsorption of sodium dodecyl sulfate (SDS) on ideal bcc-Fe surface: A first-principles investigation

Adsorption is the most significant first step for boundary lubrication film formation, catalysis and chemical synthesis processes. Nevertheless, at present, the adsorption process and its mechanism of dodecyl sulfate (DS) molecules on solid surfaces are largely conjectured. Here, adsorption properties of DS on clean ideal bcc-Fe surfaces have been computational investigated via first principles method at atomic scale. At ground state, adsorption energies Eads are ranged from -11.75 eV to -3.09 eV. Adsorption Fe-O bond is a mixture of ionic bond and covalent one. Bond strength is affected by interfacial electron transfer and its stability is related to electron gain/loss of sub-interfacial atoms. Boltzmann distributions of adsorption conformations are calculated by partition functions that only depend on relative energies, and they are used as weight coefficients to estimate mixed-Eads. The temperature-induced Fermi-softness SF is calculated to reveal relationship between Eads and SF. Considered about solvent and temperature effects, the competitive adsorption and thermal activation can reduce the difference of adsorption energy barriers between conformations. Their adsorption probabilities become closer with the distribution proportion increase of the conformations with low Eads. This can provide theoretical foundations for further understanding of boundary lubrication film formation mechanism.

Resolving Hidden Solution Conformations of Hemoglobin Using IMS-IMS on a Cyclic Instrument.

Ion mobility spectrometry-mass spectrometry (IMS-MS) experiments on a cyclic IMS instrument were used to examine heterogeneous distributions of structures found in the 15+ to 18+ charge states of the hemoglobin tetramer (Hb). The resolving power of IMS measurements is known to increase with increasing drift-region length. This effect is not significant for Hb charge states as peaks were shown to broaden with increasing drift-region length. This observation suggests that multiple structures with similar cross sections may be present. To examine this hypothesis, selections of drift time distributions were isolated and subsequently reinjected into the mobility region for additional separation. These IMS-IMS experiments demonstrate that selected regions separate further upon additional passes around the drift cell, consistent with the idea that initial resolving power was limited due to the presence of many closely related conformations. Additional variable temperature electrospray ionization (vT-ESI) experiments were conducted to study how changing the solution temperature affects solution conformations. Some features in these IMS-IMS studies were observed to change similarly with solution temperature compared to features in the single IMS distribution. Other features changed differently in the selected mobility data, indicating that solution structures that were obscured upon IMS analysis because of the complex heterogeneity of the original distribution are discernible after reducing the number of conformers that are analyzed by further IMS analysis. These results illustrate that the combination of vT-ESI with IMS-IMS is useful for resolving and exploring conformer distributions and stabilities in systems that exhibit a large degree of structural heterogeneity.

A Computational Study of a Prebiotic Synthesis of a Tripeptide: Thyrotropic Releasing Hormone (TRH)

Ab initio calculations are used to calculate the viability of a prebiotic mechanism for the synthesis of L-proteins considered as a one-dimensional cooperative system having interlocking terms involving two neighbouring amino-acid residues yielding the inter-bond energy, optimum conformation, and charge distribution leading to an estimate of the secondary structure. The prebiotic synthesis of poly amino acids is illustrated with the synthesis of a tripeptide, thyrotropic releasing hormone. The magnesium ion metalloporphyrin complex is shown to bind the prebiotic stereospecific ligand precursors of the amino acids proline, histidine, and pyroglutamic on the metal or nitrogen pyrrole sites as a two-site catalyst in their copolymerization to form Glu-His-Pro-NH2. The order of addition of the monomers is the reverse of pyroglutamylhistidinylprolamide to form the tripeptide. which is separated from the catalyst by hydrogen ions. The reactions are feasible from the overall enthalpy changes in the ZKE approximation at the HF and MP2 /6-31G* level, and with acceptable activation energies.

Effects of angular momentum and thermostat on molecular dynamics simulation of single-chain conformation in an implicit solvent

The effect of angular momentum on single-chain conformation in an implicit solvent model was investigated by molecular dynamics simulation. The distribution of the end-to-end distance depends on whether the angular momentum of the entire molecule is fixed or thermalized, and these two distributions can be transformed from the one to the other through the reweighting method. In addition, depending on the thermostat, the thermalization of the angular momentum becomes insufficient even if no constraint is imposed on the angular momentum, resulting in the distortion of the distribution of chain conformation. These results suggest the importance of the choice of thermostat that enables the thermalization of the angular momentum.

Hydrogen-Deuterium Exchange Vibrational Raman Spectroscopy Distinguishes Distinct Amyloid Polymorphs Comprising Altered Core Architecture.

Amyloid fibrils are ordered protein aggregates comprising a hydrogen-bonded central cross-β core displaying a structural diversity in their supramolecular packing arrangements within the core. Such an altered packing results in amyloid polymorphism that gives rise to morphological and biological strain diversities. Here, we show that vibrational Raman spectroscopy coupled with hydrogen/deuterium (H/D) exchange discerns the key structural features that are responsible for yielding diverse amyloid polymorphs. Such a noninvasive and label-free methodology allows us to structurally distinguish distinct amyloid polymorphs displaying altered hydrogen bonding and supramolecular packing within the cross-β structural motif. By using quantitative molecular fingerprinting and multivariate statistical analysis, we analyze key Raman bands for the protein backbone and side chains that allow us to capture the conformational heterogeneity and structural distributions within distinct amyloid polymorphs. Our results delineate the key molecular factors governing the structural diversity in amyloid polymorphs and can potentially simplify studying amyloid remodeling by small molecules.