A5085686400- Computational Drug Discovery Methods
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Crystal structures of chemical compounds
- Protein Structure and Dynamics
- Synthesis and biological activity
- Metal complexes synthesis and properties
- Crystallography and molecular interactions
- Chemical Synthesis and Analysis
- Catalytic C–H Functionalization Methods
- Synthesis and Catalytic Reactions
- Advanced Chemical Physics Studies
- Receptor Mechanisms and Signaling
- Analytical Chemistry and Chromatography
- Click Chemistry and Applications
- Spectroscopy and Quantum Chemical Studies
- Mass Spectrometry Techniques and Applications
- Monoclonal and Polyclonal Antibodies Research
- RNA and protein synthesis mechanisms
- Enzyme Structure and Function
- Sulfur-Based Synthesis Techniques
- Carbohydrate Chemistry and Synthesis
- Synthesis and Characterization of Heterocyclic Compounds
- Free Radicals and Antioxidants
- Machine Learning in Materials Science
University of Maryland, Baltimore
2016-2025
Jilin Agricultural University
2025
Hangzhou Vocational and Technical College
2007-2024
Advanced Bioscience Laboratories (United States)
2021-2024
Institute for Bioscience and Biotechnology Research
2018-2024
Shenyang Agricultural University
2023-2024
Central South University
2023
University of Baltimore
2020-2021
Chinese Academy of Medical Sciences & Peking Union Medical College
2012-2020
National Institute of Standards and Technology
2020
Abstract Presented is an extension of the CHARMM General Force Field (CGenFF) to enable modeling sulfonyl‐containing compounds. Model compounds containing chemical moieties such as sulfone, sulfonamide, sulfonate, and sulfamate were used basis for parameter optimization. Targeting high‐level quantum mechanical experimental crystal data, new parameters optimized in a hierarchical fashion designed maintain compatibility with remainder additive force field. The satisfactorily reproduced...
Diffuse large B cell lymphomas (DLBCLs) arise from proliferating cells transiting different stages of the germinal center reaction. In activated DLBCLs (ABC-DLBCLs), a class that respond poorly to current therapies, chromosomal translocations and amplification lead constitutive expression lymphoma 6 (BCL6) oncogene. The role BCL6 in maintaining these has not been investigated. Here, we designed small-molecule inhibitors display higher affinity for than its endogenous corepressor ligands...
The chitosan@copper catalyst displays high efficiency as an easily recoverable for C–S couplings and the synthesis of zolimidine.
The applicability of a computational method, Site Identification by Ligand Competitive Saturation (SILCS), to identify regions on protein surface with which different types functional groups low-molecular weight inhibitors interact is demonstrated. method involves molecular dynamics (MD) simulations in an aqueous solution chemically diverse small molecules from probability distributions fragments types, termed FragMaps, are obtained. In the present application, SILCS performed 1 M benzene...
A polarizable water model, SWM6, was developed and optimized for liquid phase simulations under ambient conditions. Building upon the previously SWM4-NDP additional sites representing oxygen lone-pairs were introduced. The geometry of is assumed to be rigid. Considering large number adjustable parameters, simulated annealing together with polynomial fitting used facilitate model optimization. new shown yield correct self-diffusion coefficient after taking system size effect into account,...
The site identification by ligand competitive saturation (SILCS) method identifies the location and approximate affinities of small molecular fragments on a target macromolecular surface performing dynamics (MD) simulations in an aqueous solution molecules representative different chemical functional groups. In this study, we introduce set to map potential interactions made neutral hydrogen bond donors acceptors charged donor acceptor addition nonpolar fragments. affinity pattern is obtained...
High-throughput measurements of phenotypic parameters in plants generate substantial data, significantly improving agricultural production optimization and breeding efficiency. However, these face several challenges, including environmental variability, sample heterogeneity, complex data processing. This study presents a method applicable to stem leaf segmentation parameter extraction during the tomato seedling stage, utilizing three-dimensional point clouds. Focusing on seedlings, was...
Small molecule empirical force fields (FFs), including the CHARMM General Force Field (CGenFF), are designed to have wide coverage of organic molecules and rapidly assign parameters not explicitly included in FF. Assignment new CGenFF is based on a trained bond-angle-dihedral charge increment linear interpolation scheme for partial atomic charges along with bonded assigned analogy using rules-based penalty score associated atom types chemical connectivity. Accordingly, accuracy related...
Solute sampling of explicit bulk-phase aqueous environments in grand canonical (GC) ensemble simulations suffer from poor convergence due to low insertion probabilities the solutes. To address this, we developed an iterative procedure involving Grand Canonical-like Monte Carlo (GCMC) and molecular dynamics (MD) simulations. Each iteration involves GCMC both solutes water followed by MD, with excess chemical potential (μex) solute oscillated attain their target concentrations simulation...
Abstract Background It has been shown in many solid tumors that the overexpression of pro-survival Bcl-2 family members Bcl-2/Bcl-xL and Mcl-1 confers resistance to a variety chemotherapeutic agents. We designed BH3 α-helix mimetic JY-1-106 engage hydrophobic BH3-binding grooves on surfaces both Bcl-xL Mcl-1. Methods JY-1-106–protein complexes were studied using molecular dynamics (MD) simulations SILCS methodology. have evaluated vitro effects by fluorescence polarization (FP) assay, an XTT...
Receptor-based pharmacophore modeling is an efficient computer-aided drug design technique that uses the structure of target protein to identify novel leads. However, most methods consider flexibility and desolvation effects in a very approximate way, which may limit their use practice. The Site-Identification by Ligand Competitive Saturation (SILCS) assisted protocol (SILCS-Pharm) was introduced recently address these issues, as SILCS naturally takes both into account using full molecular...
Chemical fragment cosolvent sampling techniques have become a versatile tool in ligand-protein binding prediction. Site-identification by ligand competitive saturation (SILCS) is one such method that maps the distribution of chemical fragments on protein as free energy fields called FragMaps. Ligands are then simulated via Monte Carlo field FragMaps (SILCS-MC) to predict their conformations and relative affinities for target protein. Application SILCS-MC using number different scoring...
Predicting relative protein–ligand binding affinities is a central pillar of lead optimization efforts in structure-based drug design.
Extensive ab initio calculations were employed to characterize stable conformers of gaseous arginine, both the canonical and zwitterionic tautomers. Step-by-step geometry optimizations possible single-bond rotamers at B3LYP/6-31G(d), B3LYP/6-31++G(d,p), MP2/6-31++G(d,p) levels yield numerous structures that are more than any known ones. The final electronic energies determined CCSD/6-31++G(d,p) level. lowest lower existing values by 2.0 2.3 kcal/mol, respectively. relative energies,...
Occluded ligand-binding pockets (LBP) such as those found in nuclear receptors (NR) and G-protein coupled (GPCR) represent a significant opportunity challenge for computer-aided drug design. To determine free energies maps of functional groups these LBPs, Grand-Canonical Monte Carlo/Molecular Dynamics (GCMC/MD) strategy is combined with the Site Identification by Ligand Competitive Saturation (SILCS) methodology. SILCS-GCMC/MD shown to map group affinity patterns that recapitulate locations...
We have previously reported on the functional interaction of Lipid II with human alpha-defensins, a class antimicrobial peptides. is an essential precursor for bacterial cell wall biosynthesis and ideal validated target natural antibiotic compounds. Using combination structural, in silico analyses, we present here molecular basis defensin-Lipid binding. Based complex Human Neutrophil peptide-1, could identify characterize chemically diverse low-molecular weight compounds that mimic...
We report a novel synthesis of phenanthridinones from N-methoxybenzamides using an oxidative C-H amidation reaction at room temperature in open air with modest to excellent yields. This method demonstrated unprecedented substrate scope. In particular, it solved the long-standing challenge sterically demanding substitutions.
Enveloped viruses depend on the host endoplasmic reticulum (ER) quality control (QC) machinery for proper glycoprotein folding. The (ERQC) enzyme α-glucosidase I (α-GluI) is an attractive target developing broad-spectrum antivirals. We synthesized 28 inhibitors designed to interact with all four subsites of α-GluI active site. These are derivatives iminosugars 1-deoxynojirimycin (1-DNJ) and valiolamine. Crystal structures ER bound 25 1-DNJ three valiolamine revealed basis inhibitory potency....
An improvement in the computational efficiency of polarizable force field simulations is made through development a Drude water model, SWM3, combination with use Lennard-Jones Particle Mesh Ewald (LJPME) for treatment long-range LJ interactions. The experimental bulk properties, density, heat vaporization, dielectric constant, and self-diffusion constant SWM3 model are accurately replicated at ambient condition. temperature dependence properties also captured except density. Microscopic such...