Deciphering single-cell 3D chromatin structure using scCTG.

Sequencing-based Hi-C technology has been widely used to study the three-dimensional structure of chromatin. More recently, the development of single-cell Hi-C technology has enabled the study of chromatin structural variations between individual cells. However, single-cell Hi-C data are often highly sparse, necessitating the use of imputation algorithms to address insufficient sampling.

Real-Time TDDFT Using Noncollinear Functionals.

Recently, we proposed a method to generalize collinear functionals to noncollinear functionals, called multicollinear approach, which has been applied in density functional theory (DFT) and linear-response time-dependent DFT (TDDFT) for the ground state and excited states calculations, respectively. In this work, we demonstrate the application of this method in real-time TDDFT by simulating electronic absorption spectra, Rabi resonance, and precession of a two-magnetic center system. Thanks to the nonvanishing local exchange-correlation torque provided by multicollinear functionals, research into the torques in the evolution of magnetization vector is carried out, which is useful for the exploration on spin dynamics.

DSDPFlex: Flexible-Receptor Docking with GPU Acceleration.

Molecular docking is an essential tool in structure-based drug discovery, widely utilized to model ligand-protein interactions and enrich potential hits. Among the different docking strategies, semiflexible docking (rigid-receptor and flexible-ligand model) is the most popular, benefiting from its balance of docking accuracy and speed. However, this approach ignores the conformational changes of proteins and hence demands suitable protein conformations as input.

Atomistic Insights into Sequence-Mediated Spontaneous Association of Short RNA Chains.

RNA-RNA association and phase separation appear to be essential for the assembly of stress granules and underlie RNA foci formation in repeat expansion disorders. RNA molecules are found to play a significant role in gene-regulatory functions via condensate formation among themselves or with RNA-binding proteins. The interplay between driven versus spontaneous processes is likely to be an important factor for controlling the formation of RNA-mediated biomolecular condensate.

Radiotherapy-triggered reduction of platinum-based chemotherapeutic prodrugs in tumours.

Pt(II) drugs are a widely used chemotherapeutic, yet their side effects can be severe. Here we show that the radiation-induced reduction of Pt(IV) complexes to cytotoxic Pt(II) drugs is rapid, efficient and applicable in water, that it is mediated by hydrated electrons from water radiolysis and that the X-ray-induced release of Pt(II) drugs from an oxaliplatin prodrug in tumours inhibits their growth, as we show with nearly complete tumour regression in mice with subcutaneous human tumour xenografts. The combination of low-dose radiotherapy with a Pt(IV)-based antibody-trastuzumab conjugate led to the tumour-selective release of the chemotherapeutic in mice and to substantial therapeutic benefits.

Generating High-Precision Force Fields for Molecular Dynamics Simulations to Study Chemical Reaction Mechanisms Using Molecular Configuration Transformer.

Theoretical studies on chemical reaction mechanisms have been crucial in organic chemistry. Traditionally, calculating the manually constructed molecular conformations of transition states for chemical reactions using quantum chemical calculations is the most commonly used method. However, this way is heavily dependent on individual experience and chemical intuition.

Structural and dynamical aspect of DNA motif sequence specific binding of AP-1 transcription factor.

Activator protein-1 (AP-1) comprises one of the largest and most evolutionary conserved families of ubiquitous eukaryotic transcription factors that act as a pioneer factor. Diversity in DNA binding interaction of AP-1 through a conserved basic-zipper (bZIP) domain directs in-depth understanding of how AP-1 achieves its DNA binding selectivity and consequently gene regulation specificity. Here, we address the structural and dynamical aspects of the DNA target recognition process of AP-1 using microsecond-long atomistic simulations based on the structure of the human AP-1 FosB/JunD bZIP-DNA complex.

Steric repulsion introduced by loop constraints modulates the microphase separation of chromatins.

Within the confines of a densely populated cell nucleus, chromatin undergoes intricate folding, forming loops, domains, and compartments under the governance of topological constraints and phase separation. This coordinated process inevitably introduces interference between different folding strategies. In this study, we model interphase chromatins as block copolymers with hetero-hierarchical loops within a confined system.

PMC-IZ: A Simple Algorithm for the Electrostatics Calculation in Slab Geometric Molecular Dynamics Simulations.

Slab geometric systems are widely utilized in molecular simulations. However, an efficient, straightforward, and accurate method for calculating electrostatic interactions in these systems for molecular dynamics (MD) simulations is still needed. This review introduces a PME-like approach called PMC-IZ, specifically designed for slab geometric systems.

Nanoscale one-dimensional close packing of interfacial alkali ions driven by water-mediated attraction.

The permeability and selectivity of biological and artificial ion channels correlate with the specific hydration structure of single ions. However, fundamental understanding of the effect of ion-ion interaction remains elusive. Here, via non-contact atomic force microscopy measurements, we demonstrate that hydrated alkali metal cations (Na and K) at charged surfaces could come into close contact with each other through partial dehydration and water rearrangement processes, forming one-dimensional chain structures.

Unsupervisedly Prompting AlphaFold2 for Accurate Few-Shot Protein Structure Prediction.

Data-driven predictive methods that can efficiently and accurately transform protein sequences into biologically active structures are highly valuable for scientific research and medical development. Determining an accurate folding landscape using coevolutionary information is fundamental to the success of modern protein structure prediction methods. As the state of the art, AlphaFold2 has dramatically raised the accuracy without performing explicit coevolutionary analysis.

Action at a distance: organic cation induced long range organization of interfacial water enhances hydrogen evolution and oxidation kinetics.

Engineering efficient electrode-electrolyte interfaces for the hydrogen evolution and oxidation reactions (HOR/HER) is central to the growing hydrogen economy. Existing descriptors for HOR/HER catalysts focused on species that could directly impact the immediate micro-environment of surface-mediated reactions, such as the binding energies of adsorbates. In this work, we demonstrate that bulky organic cations, such as tetrapropyl ammonium, are able to induce a long-range structure of interfacial water molecules and enhance the HOR/HER kinetics even though they are located outside the outer Helmholtz plane.

Diffusion-enhanced characterization of 3D chromatin structure reveals its linkage to gene regulatory networks and the interactome.

The interactome networks at the DNA, RNA, and protein levels are crucial for cellular functions, and the diverse variations of these networks are heavily involved in the establishment of different cell states. We have developed a diffusion-based method, Hi-C to geometry (CG), to obtain reliable geometric information on the chromatin from Hi-C data. CG produces a consistent and reproducible framework for the 3D genomic structure and provides a reliable and quantitative understanding of the alterations of genomic structures under different cellular conditions.

DSDP: A Blind Docking Strategy Accelerated by GPUs.

Virtual screening, including molecular docking, plays an essential role in drug discovery. Many traditional and machine-learning-based methods are available to fulfill the docking task. However, the traditional docking methods are normally extensively time-consuming, and their performance in blind docking remains to be improved.

Artificial Intelligence Enhanced Molecular Simulations.

Molecular simulations, which simulate the motions of particles according to fundamental laws of physics, have been applied to a wide range of fields from physics and materials science to biochemistry and drug discovery. Developed for computationally intensive applications, most molecular simulation software involves significant use of hard-coded derivatives and code reuse across various programming languages. In this Review, we first align the relationship between molecular simulations and artificial intelligence (AI) and reveal the coherence between the two.

Investigating the Activation Mechanism Differences between Human and Mouse cGAS by Molecular Dynamics Simulations.

Cyclic GMP-AMP synthase (cGAS) has been widely investigated as a drug target for its crucial role in innate immunity. However, the inhibitors designed using mouse model were often shown to be ineffective for humans. This outcome indicates that the activation mechanisms of human and mouse cGAS (mcGAS) are different.

Noncollinear and Spin-Flip TDDFT in Multicollinear Approach.

Time-dependent density functional theory (TDDFT) is one of the most important tools for investigating the excited states of electrons. The TDDFT calculation for spin-conserving excitation, where collinear functionals are sufficient, has obtained great success and has become routine. However, TDDFT for noncollinear and spin-flip excitations, where noncollinear functionals are needed, is less widespread and still a challenge nowadays.

Characterization of network hierarchy reflects cell state specificity in genome organization.

Dynamic chromatin structure acts as the regulator of transcription program in crucial processes including cancer and cell development, but a unified framework for characterizing chromatin structural evolution remains to be established. Here, we performed graph inferences on Hi-C data sets and derived the chromatin contact networks. We discovered significant decreases in information transmission efficiencies in chromatin of colorectal cancer (CRC) and T-cell acute lymphoblastic leukemia (T-ALL) compared to corresponding normal controls through graph statistics.

Microscopic model on indoor propagation of respiratory droplets.

Indoor propagation of airborne diseases is yet poorly understood. Here, we theoretically study a microscopic model based on the motions of virus particles in a respiratory microdroplet, responsible for airborne transmission of diseases, to understand their indoor propagation. The virus particles are driven by a driving force that mimics force due to gushing of air by devices like indoor air conditioning along with the gravity.

Sequence-Specific Structural Features and Solvation Properties of Transcription Factor Binding DNA Motifs: Insights from Molecular Dynamics Simulation.

Sequence-specific recognition of transcription factor (TF) binding motifs in the target site of DNA over the vast amount of non-target DNA is of primary importance for the transcriptional regulation of gene expression by the TFs. Binding of TFs to the target site of DNA relies not only on the direct contact formation but also on the structural and conformational features of DNA. Recognition of DNA structural features or shape readout by proteins is an important factor in the context of TF-DNA interaction.

Multi-scale gene regulation mechanism: Spatiotemporal transmission of genetic information.

Gene expression is regulated by many factors, including transcription factors, chromatin three-dimensional topology, modifications of DNA and histone proteins, and non-coding RNAs. The execution of these complex mechanisms requires an effectively coordinated regulation system. In this review, we emphasize that the multi-scale heterogeneous DNA sequence plays a fundamental and important role for gene expression activity and usage of different means of epigenetic regulation.

Accelerating supramolecular aggregation by molecular sliding.

Diffusion-based translocation along DNA or RNA molecules is essential for genome regulatory proteins to execute their biological functions. The reduced dimensionality of the searching process makes the proteins bind specific target sites at a "faster-than-diffusion-controlled rate". We herein report a photoresponsive slider-track diffusion system capable of self-assembly rate acceleration, which consists of (-)-camphorsulfonic acid, 4-(4'--octoxylphenylazo)benzenesulfonic acid, and isotactic poly(2-vinylpyridine).