Since the influential work of ten Wolde, Ruiz-Montero, and Frenkel [Phys. Rev. Lett. 75, 2714 (1995)], crystal nucleation from a Lennard-Jones fluid has been regarded as paradigmatic example metastable ordering at surface critical nucleus. We apply seven commonly used local structure detection algorithms to characterize nuclei obtained transition path sampling simulations. The polymorph composition these varies significantly depending on algorithm used. Our results indicate that one should...

With the continual improvement of computing hardware and algorithms, simulations have become a powerful tool for understanding all sorts (bio)molecular processes. To handle large simulation data sets to accelerate slow, activated transitions, condensed set descriptors, or collective variables (CVs), is needed discern relevant dynamics that describes molecular process interest. However, proposing an adequate CVs can capture intrinsic reaction coordinate transition often extremely difficult....

Abstract Molecular dynamics (MD) simulations can provide detailed insights into complex molecular systems, such as DNA, at high resolution in space and time. Using current computer architectures, time scales of tens microseconds are feasible with contemporary all‐atom force fields. However, these timescales insufficient to accurately characterize large conformational transitions DNA compare calculations experimental data. This review discusses the advantages drawbacks two simulation...

Study of complex activated molecular transitions by dynamics (MD) simulation can be a daunting task, especially when little knowledge is available on the reaction coordinate describing mechanism process. Here, we assess path-metadynamics enhanced sampling approach in combination with force field and ab initio [density functional theory (DFT)] MD simulations conformational chemical that require three or more collective variables (CVs) to describe processes. We show method efficiently...

Optimizing the design and synthesis of complex crystal structures presents pivotal opportunities challenges in materials design. While recent computational advances inverse have proven effective for simpler crystals, their extension to intricate such as zeolites remains challenging. In this work, we introduce an efficient robust workflow specifically tailored predictive a broad range phases. By integrating evolutionary parameter optimization strategy with enhanced sampling molecular dynamics...

The biological functions of natural polyelectrolytes are strongly influenced by the presence ions, which bind to polymer chains and thereby modify their properties. Although impact such modifications is well recognized, a detailed molecular picture binding process mechanisms that drive subsequent structural changes in lacking. Here, we study mechanism condensation calcium, divalent cation, on hyaluronan, ubiquitous human tissues. By combining two-dimensional infrared spectroscopy experiments...

Abstract DNA predominantly contains Watson–Crick (WC) base pairs, but a non-negligible fraction of pairs are in the Hoogsteen (HG) hydrogen bonding motif at any time. In HG, purine is rotated ∼180° relative to WC motif. The transitions between and HG may play role recognition replication, difficult investigate experimentally because they occur quickly, only rarely. To gain insight into mechanisms for this process, we performed transition path sampling simulations on model nucleotide sequence...

Hoogsteen (HG) base pairing is characterized by a 180° rotation of the purine with respect to Watson-Crick-Franklin (WCF) motif. Recently, it has been found that both conformations coexist in dynamical equilibrium and several biological functions require HG pairs. This relevance motivated experimental computational investigations base-pairing transition. However, systematic simulation sequence variations remained out reach. Here, we employ advanced path-based methods perform unprecedented...

Boltzmann generators (BGs) are now recognized as forefront generative models for sampling equilibrium states of many-body systems in the canonical ensemble, well calculating corresponding Helmholtz free energy. Furthermore, BGs can potentially provide a notable improvement efficiency compared to conventional techniques such molecular dynamics (MD) and Monte Carlo (MC) methods. By from clustered latent space, circumvent free-energy barriers overcome rare-event problem. However, one major...

The development of new materials typically involves a process trial and error, guided by insights from past experimental theoretical findings. inverse design approach for soft-matter systems has the potential to optimize specific physical parameters, such as particle interactions, shape, or composition packing fraction. This optimization aims facilitate spontaneous formation target structures through self-assembly. In this study, we expand upon recently introduced protocol monodisperse...

The carboxyl (COOH) side chain groups of amino acids, such as aspartic acid, play an important role in biochemical processes, including enzymatic proton transport. In many theoretical studies, it was found that the (bio)chemical reactivity group strongly depends on conformation this group. Interestingly, up to now there has been no experimental investigation geometry and stability different COOH conformers under biorelevant conditions. Here, we investigate conformational isomerism N-acetyl...

Abstract Blue light-using flavin (BLUF) proteins are light-sensors that regulate responsive movement, gene expression and enzyme activity in diverse organisms. Their signaling times range from seconds to minutes, indicating a uniquely flexible dark-state recovery mechanism. Unlike other light-sensors, the chromophore is non-covalently bonded protein. Hence, switching occurs via change protein-flavin hydrogen-bond network, involving conserved residues transferring protons, tautomerizing,...

The development of new materials typically involves a process trial and error, guided by insights from past experimental theoretical findings. inverse design approach for soft-matter systems has the potential to optimize specific physical parameters such as particle interactions, shape, or composition packing fraction. This optimization aims facilitate spontaneous formation target structures through self-assembly. In this study, we expand upon recently introduced protocol monodisperse...

Optimizing the synthesis of zeolites and exploring novel frameworks offer pivotal opportunities challenges in materials design. While inverse design proves highly effective for simpler crystals, its application to intricate structures like poses severe challenges. Here, we introduce an innovative workflow tailored efficiently reproduce target zeolite a binary coarse-grained model using enhanced sampling molecular dynamics simulations. This integrates evolutionary parameter optimization...

Since the influential work of ten Wolde, Ruiz-Montero, and Frenkel [Phys. Rev. Lett. 75, 2714 (1995)], crystal nucleation from a Lennard-Jones fluid has been regarded as paradigmatic example metastable ordering at surface critical nucleus. We apply seven commonly used local structure detection algorithms to characterize nuclei obtained transition path sampling simulations. The polymorph composition these varies significantly depending on algorithm used. Our results indicate that one should...

Abstract Hoogsteen (HG) base-pairing is characterized by a 180° rotation of the purine base with respect to Watson-Crick-Franklin (WCF) motif. Recently, it has been found that both conformations coexist in dynamical equilibrium and several biological functions require HG pairs. This relevance motivated experimental computational investigations transition. However, systematic simulation sequence variations remained out reach. Here, we employ advanced path-based methods perform unprecedented...

ABSTRACT The biological functions of natural polyelectrolytes are strongly influenced by the presence ions, which bind to polymer chains and thereby modify their properties. Although impact such modifications is well-recognized, a detailed molecular picture binding process mechanisms that drive subsequent structural changes in lacking. Here, we study mechanism condensation calcium, divalent cation, on hyaluronan, ubiquitous human tissues. By combining two-dimensional infrared spectroscopy...

We present a molecular simulation method to simultaneously find multiple transition pathways, and their associated free-energy profiles. The scheme extends path-metadynamics (PMD) [Phys. Rev. Lett. 109, 020601 (2012)] with paths repulsive walkers (multiPMD). illustrate multiPMD for two C7eq-to-C7ax in Ace-Ala-Nme six PPII-to-PPII Ace-(Pro)4-Nme. also show render an interpretable "PathMap", showing the free energy ridges between paths, as well branching merging of channels. MultiPMD is...