Rare-Event Sampling using a Reinforcement Learning-Based Weighted Ensemble Method.

Despite the power of path sampling strategies in enabling simulations of rare events, such strategies have not reached their full potential. A common challenge that remains is the identification of a progress coordinate that captures the slow relevant motions of a rare event. Here we have developed a weighted ensemble (WE) path sampling strategy that exploits reinforcement learning to automatically identify an effective progress coordinate among a set of potential coordinates during a simulation.

WEDAP: A Python Package for Streamlined Plotting of Molecular Simulation Data.

Given the growing interest in path sampling methods for extending the time scales of molecular dynamics (MD) simulations, there has been great interest in software tools that streamline the generation of plots for monitoring the progress of large-scale simulations. Here, we present the WEDAP Python package for simplifying the analysis of data generated from either conventional MD simulations or the weighted ensemble (WE) path sampling method, as implemented in the widely used WESTPA software package. WEDAP facilitates (i) the parsing of WE simulation data stored in highly compressed, hierarchical HDF5 files and (ii) incorporates trajectory weights from WE simulations into all generated plots.

WEDAP: A Python Package for Streamlined Plotting of Molecular Simulation Data.

Given the growing interest in path sampling methods for extending the timescales of molecular dynamics (MD) simulations, there has been great interest in software tools that streamline the generation of plots for monitoring the progress of large-scale simulations. Here, we present the WEDAP Python package for simplifying the analysis of data generated from either conventional MD simulations or the weighted ensemble (WE) path sampling method, as implemented in the widely used WESTPA software package. WEDAP facilitates (i) the parsing of WE simulation data stored in highly compressed, hierarchical HDF5 files, and (ii) incorporates trajectory weights from WE simulations into all generated plots.

Targeting spike glycans to inhibit SARS-CoV2 viral entry.

SARS-CoV-2 spike harbors glycans which function as ligands for lectins. Therefore, it should be possible to exploit lectins to target SARS-CoV-2 and inhibit cellular entry by binding glycans on the spike protein. agglutinin (BOA) is an antiviral lectin that interacts with viral glycoproteins via N-linked high mannose glycans.

Ligand-Capped Cobalt(II) Multiplies the Value of the Double-Histidine Motif for PCS NMR Studies.

In structural studies by NMR, pseudocontact shifts (PCSs) provide both angular and distance information. For proteins, incorporation of a di-histidine (diHis) motif, coordinated to Co, has emerged as an important tool to measure PCS. Here, we show that using different Co(II)-chelating ligands, such as nitrilotriacetic acid (NTA) and iminodiacetic acid (IDA), resolves the isosurface ambiguity of Co-diHis and yields orthogonal PCS data sets with different Δχ-tensors for the same diHis-bearing protein.

Targeting Spike Glycans to Inhibit SARS-CoV2 Viral Entry.

SARS-CoV-2 Spike harbors glycans which function as ligands for lectins. Therefore, it should be possible to exploit lectins to target SARS-CoV-2 and inhibit cellular entry by binding glycans on the Spike protein. agglutinin (BOA) is an antiviral lectin that interacts with viral glycoproteins via N-linked high mannose glycans.

Development and Validation of Fluorinated, Aromatic Amino Acid Parameters for Use with the AMBER ff15ipq Protein Force Field.

We developed force field parameters for fluorinated, aromatic amino acids enabling molecular dynamics (MD) simulations of fluorinated proteins. These parameters are tailored to the AMBER ff15ipq protein force field and enable the modeling of 4, 5, 6, and 7F-tryptophan, 3F- and 3,5F-tyrosine, and 4F- or 4-CF-phenylalanine. The parameters include 181 unique atomic charges derived using the implicitly polarized charge (IPolQ) scheme in the presence of SPC/E explicit water molecules and 9 unique bond, angle, or torsion terms.

A twist in the road less traveled: The AMBER ff15ipq-m force field for protein mimetics.

We present a new force field, AMBER ff15ipq-m, for simulations of protein mimetics in applications from therapeutics to biomaterials. This force field is an expansion of the AMBER ff15ipq force field that was developed for canonical proteins and enables the modeling of four classes of artificial backbone units that are commonly used alongside natural α residues in blended or "heterogeneous" backbones: chirality-reversed D-α-residues, the C-methylated α-residue Aib, homologated β-residues (β) bearing proteinogenic side chains, and two cyclic β residues (β; APC and ACPC). The ff15ipq-m force field includes 472 unique atomic charges and 148 unique torsion terms.