Decoding Solubility Signatures from Amyloid Monomer Energy Landscapes.

This study investigates the energy landscapes of amyloid monomers, which are crucial for understanding protein misfolding mechanisms in Alzheimer's disease. While proteins possess inherent thermodynamic stability, environmental factors can induce deviations from native folding pathways, leading to misfolding and aggregation, phenomena closely linked to solubility. Using the UNOPTIM program, which integrates the UNRES potential into the Cambridge energy landscape framework, we conducted single-ended transition state searches and employed discrete path sampling to compute kinetic transition networks starting from PDB structures.

Energy Landscapes for the Unitary Coupled Cluster Ansatz.

The unitary coupled cluster (UCC) approach has been one of the most popular wavefunction parametrizations for the variational quantum eigensolver due to the relative ease of optimization compared to hardware-efficient ansätze. In this contribution, we explore the energy landscape of the unitary coupled cluster singles and doubles (UCCSD) wavefunction for two commonly employed benchmark systems, lithium hydride and the nitrogen dimer. We investigate the organization of the solution space in terms of local minima and show how it changes as the number and order of operators of the UCC ansatz are varied.

Investigation into the effect of phenylalanine gating on anaerobic haem breakdown using the energy landscape approach.

We have recently demonstrated a novel anaerobic NADH-dependent haem breakdown reaction, which is carried out by a range of haemoproteins. The Yersinia enterocolitica protein, HemS, is the focus of further research presented in the current paper. Using conventional experimental methods, bioinformatics, and energy landscape theory (ELT), we provide new insight into the mechanism of the novel breakdown process.

Effect of Exact Exchange on the Energy Landscape in Self-Consistent Field Theory.

Density functional approximations can reduce the spin symmetry breaking observed for self-consistent field (SCF) solutions compared to Hartree-Fock theory, but the amount of exact Hartree-Fock (HF) exchange appears to be a key determinant in broken symmetry. To elucidate the precise role of exact exchange, we investigate the energy landscape of unrestricted Hartree-Fock and Kohn-Sham density functional theory for benzene and square cyclobutadiene, which provide paradigmatic examples of closed-shell and open-shell electronic structures, respectively. We find that increasing the amount of exact exchange leads to more local SCF minima, which can be characterized as combinatorial arrangements of unpaired electrons in the carbon π system.

A pseudo-cubic metal-organic cage with conformationally switchable faces for dynamically adaptive guest encapsulation.

The creation of hosts capable of accommodating different guest molecules may enable these hosts to play useful roles in chemical purifications, among other applications. Metal-organic cages are excellent hosts for various guests, but they generally incorporate rigid structural units that hinder dynamic adaptation to specific guests. Here we report a conformationally adaptable pseudo-cubic cage that can dynamically increase its cavity volume to fit guests with differing sizes.

Double-Bridging Increases the Stability of Zinc(II) Metal-Organic Cages.

A key feature of coordination cages is the dynamic nature of their coordinative bonds, which facilitates the synthesis of complex polyhedral structures and their post-assembly modification. However, this dynamic nature can limit cage stability. Increasing cage robustness is important for real-world use cases.

The energy landscape of Aβ: a funnel to disorder for the monomer becomes a folding funnel for self-assembly.

The aggregation of amyloid-β (Aβ) peptides, particularly Aβ, plays a key role in Alzheimer's disease pathogenesis. In this study, we investigate how dimerisation transforms the free energy surface (FES) of the Aβ monomer when it interacts with another Aβ peptide. We find that the monomer FES is a structurally inverted funnel with a disordered state at the global minimum.

Design principles for energy transfer in the photosystem II supercomplex from kinetic transition networks.

Photosystem II (PSII) has the unique ability to perform water-splitting. With light-harvesting complexes, it forms the PSII supercomplex (PSII-SC) which is a functional unit that can perform efficient energy conversion, as well as photoprotection, allowing photosynthetic organisms to adapt to the naturally fluctuating sunlight intensity. Achieving these functions requires a collaborative energy transfer network between all subunits of the PSII-SC.

COVID-19 immunization status in children compared to their parents: a retrospective review at an upstate NY medicine/pediatrics practice.

Background: This study aimed to investigate the relationship between parent and child COVID-19 immunization series completion using vaccine records.

Methods: A cross-sectional chart review was performed on parent and child patients at the Albany Medical Center Internal Medicine and Pediatrics practice. Patient and parent demographic data, COVID-19 immunization status, and health care worker status was collected.

Energy landscapes for clusters of hexapeptides.

We present the results for energy landscapes of hexapeptides obtained using interfaces to the Large-scale Atomic/Molecular Massively Parallel Simulator (LAMMPS) program. We have used basin-hopping global optimization and discrete path sampling to explore the landscapes of hexapeptide monomers, dimers, and oligomers containing 10, 100, and 200 monomers modeled using a residue-level coarse-grained potential, Mpipi, implemented in LAMMPS. We find that the dimers of peptides containing amino acid residues that are better at promoting phase separation, such as tyrosine and arginine, have melting peaks at higher temperature in their heat capacity compared to phenylalanine and lysine, respectively.

Vibrational Energy Landscapes and Energy Flow in GPCRs.

We construct and analyze disconnectivity graphs to provide the first graphical representation of the vibrational energy landscape of a protein, in this study βAR, a G-protein coupled receptor (GPCR), in active and inactive states. The graphs, which indicate the relative free energy of each residue and the minimum free energy barriers for energy transfer between them, reveal important composition, structural and dynamic properties that mediate the flow of energy. Prolines and glycines, which contribute to GPCR plasticity and function, are identified as bottlenecks to energy transport along the backbone from which alternative pathways for energy transport via nearby noncovalent contacts emerge, seen also in the analysis of first passage time (FPT) distributions presented here.

Oscillatory Active State of a Pd Nanocatalyst Identified by Capture of the Instantaneous Structure-Activity Change at the Atomic Scale.

Identifying the active phase with the highest activity, which is long-believed to be a steady state of the catalyst, is the basis of rational design of heterogeneous catalysis. In this work, we performed detailed investigations, successfully capturing the instantaneous structure-activity change in oscillating Pd nanocatalysts during methane oxidation, which reveals an unprecedented oscillatory active state. Combining quantitative environmental transmission electron microscopy and highly sensitive online mass spectrometry, we identified two distinct phases for the reaction: one where the Pd nanoparticles refill with oxygen, and the other, a period of abrupt pumping of oxygen and boosted methane oxidation within about 1 s.

Going for Gold(-Standard): Attaining Coupled Cluster Accuracy in Oxide-Supported Nanoclusters.

The structure of oxide-supported metal nanoclusters plays an essential role in their sharply enhanced catalytic activity over that of bulk metals. Simulations provide the atomic-scale resolution needed to understand these systems. However, the sensitive mix of metal-metal and metal-support interactions, which govern their structure, puts stringent requirements on the method used, requiring calculations beyond standard density functional theory (DFT).

Energy Landscapes and Structural Ensembles of Glucagon-like Peptide-1 Monomers.

While GLP-1 and its analogues are important pharmaceutical agents in the treatment of type 2 diabetes and obesity, their susceptibility to aggregate into amyloid fibrils poses a significant safety issue. Many factors may contribute to the aggregation propensity, including pH. While it is known that the monomeric structure of GLP-1 has a strong impact on primary nucleation, probing its diverse structural ensemble is challenging.

100 Years of the Lennard-Jones Potential.

It is now 100 years since Lennard-Jones published his first paper introducing the now famous potential that bears his name. It is therefore timely to reflect on the many achievements, as well as the limitations, of this potential in the theory of atomic and molecular interactions, where applications range from descriptions of intermolecular forces to molecules, clusters, and condensed matter.

Multilevel Framework for Analysis of Protein Folding Involving Disulfide Bond Formation.

In this study, a three-layered multicenter ONIOM approach is implemented to characterize the naive folding pathway of bovine pancreatic trypsin inhibitor (BPTI). Each layer represents a distinct level of theory, where the initial layer, encompassing the entire protein, is modeled by a general all-atom force-field GFN-FF. An intermediate electronic structure layer consisting of three multicenter fragments is introduced with the state-of-the-art semiempirical tight-binding method GFN2-TB.

Detection of medically relevant volatile organic compounds with graphene field-effect transistors and separated by low-frequency spectral and time signatures.

Exhaled human breath contains a mixture of gases including nitrogen, oxygen, carbon dioxide, water vapour and low molecular weight volatile organic compounds (VOCs). Different VOCs detected in human breath condensate have been recently related to several metabolic processes occurring inside body tissues in the pathological state, as candidate biomarkers for monitoring conditions such as lung injury, airway inflammation, immunity dysfunction, infection, and cancer. Current techniques for detecting these compounds include several types of mass spectroscopy, which are highly costly, time-consuming and dependent on trained personnel for sample analysis.

Analysis and interpretation of first passage time distributions featuring rare events.

In this contribution we consider theory and associated computational tools to treat the kinetics associated with competing pathways on multifunnel energy landscapes. Multifunnel landscapes are associated with molecular switches and multifunctional materials, and are expected to exhibit multiple relaxation time scales and associated thermodynamic signatures in the heat capacity. Our focus here is on the first passage time distribution, which is encoded in a kinetic transition network containing all the locally stable states and the pathways between them.

Combining experiment and energy landscapes to explore anaerobic heme breakdown in multifunctional hemoproteins.

To survive, many pathogens extract heme from their host organism and break down the porphyrin scaffold to sequester the Fe ion a heme oxygenase. Recent studies have revealed that certain pathogens can anaerobically degrade heme. Our own research has shown that one such pathway proceeds NADH-dependent heme degradation, which has been identified in a family of hemoproteins from a range of bacteria.

Energy landscapes for proteins described by the UNRES coarse-grained potential.

The self-assembly of proteins is encoded in the underlying potential energy surface (PES), from which we can predict structure, dynamics, and thermodynamic properties. However, the corresponding analysis becomes increasingly challenging with larger protein sizes, due to the computational time required, which grows significantly with the number of atoms. Coarse-grained models offer an attractive approach to reduce the computational cost.

Energy landscapes and heat capacity signatures for peptides correlate with phase separation propensity.

Phase separation plays an important role in the formation of membraneless compartments within the cell and intrinsically disordered proteins with low-complexity sequences can drive this compartmentalisation. Various intermolecular forces, such as aromatic-aromatic and cation-aromatic interactions, promote phase separation. However, little is known about how the ability of proteins to phase separate under physiological conditions is encoded in their energy landscapes and this is the focus of the present investigation.

Global analysis of energy landscapes for materials modeling: A test case for C60.

In this contribution, we employ computational tools from the energy landscape approach to test Gaussian Approximation Potentials (GAPs) for C60. In particular, we apply basin-hopping global optimization and explore the landscape starting from the low-lying minima using discrete path sampling. We exploit existing databases of minima and transition states harvested from previous work using tight-binding potentials.

Exploring energy landscapes for solid-state systems with variable cells at the extended tight-binding level.

The design of novel materials requires a theoretical understanding of dynamical processes in the solid state, including polymorphic transitions and associated pathways. The organization of the potential energy landscape plays a crucial role in such processes, which may involve changes in the periodic boundaries. This study reports the implementation of a general framework for periodic condensed matter systems in our energy landscape analysis software, allowing for variation in both the unit cell and atomic positions.

On the Mechanism of Polaritonic Rate Suppression from Quantum Transition Paths.

Polariton chemistry holds promise for facilitating mode-selective chemical reactions, but the underlying mechanism behind the rate modifications observed under strong vibrational coupling is not well understood. Using the recently developed quantum transition path theory, we have uncovered a mechanism of resonant suppression of a thermal reaction rate in a simple model polaritonic system consisting of a reactive mode in a bath confined to a lossless microcavity with a single photon mode. We observed the formation of a polariton during rate-limiting transitions on reactive pathways and identified the concomitant rate suppression as being due to hybridization between the reactive mode and the cavity mode, which inhibits bath-mediated tunneling.