Publication Category: Molecular Modeling

  • Mechanism of Biomolecular Recognition of Trimethyllysine by the Fluorinated Aromatic Cage of KDM5A PHD3 Finger

    Commun Chem 3 (1), 1-12

    The understanding of biomolecular recognition of posttranslationally modified histone proteins is centrally important to the histone code hypothesis. Despite extensive binding and structural studies on the readout of histones, the molecular language by which posttranslational modifications on histone proteins are read remains poorly understood. Here we report physical-organic chemistry studies on the recognition of the

  • A Water-Bridged Cysteine-Cysteine Redox Regulation Mechanism in Bacterial Protein Tyrosine Phosphatases

    Chem 3 (4), 665-677

    The emergence of multidrug-resistant Mycobacterium tuberculosis(Mtb) strains highlights the need to develop more efficacious and potent drugs. However, this goal is dependent on a comprehensive understanding of Mtb virulence protein effectors at the molecular level. Here, we used a post-expression cysteine (Cys)-to-dehydrolanine (Dha) chemical editing strategy to identify a water-mediated motif that modulates accessibility of the protein tyrosinephosphatase A (PtpA) catalytic pocket.

  • Chemical Basis for the Recognition of Trimethyllysine by Epigenetic Reader Proteins

    Nat Commun 6 (1), 1-12

    A large number of structurally diverse epigenetic reader proteins specifically recognize methylated lysine residues on histone proteins. Here we describe comparative thermodynamic, structural and computational studies on recognition of the positively charged natural trimethyllysine and its neutral analogues by reader proteins. This work provides experimental and theoretical evidence that reader proteins predominantly recognize trimethyllysine via

  • Improving Docking Results via Reranking of Ensembles of Ligand Poses in Multiple X-ray Protein Conformations with MM-GBSA

    J. Chem. Inf. Model. 2014, 54, 10, 2697–2717

    There is a tendency in the literature to be critical of scoring functions when docking programs perform poorly. The assumption is that existing scoring functions need to be enhanced or new ones developed in order to improve the performance of docking programs for tasks such as pose prediction and virtual screening. However, failures can result

  • Novel Procedure for Modeling Ligand/Receptor Induced Fit Effects

    J. Med. Chem. 2006, 49, 2, 534–553

    Most ReadWidely Cited

    We present a novel protein−ligand docking method that accurately accounts for both ligand and receptor flexibility by iteratively combining rigid receptor docking (Glide) with protein structure prediction (Prime) techniques. While traditional rigid-receptor docking methods are useful when the receptor structure does not change substantially upon ligand binding, success is limited when the protein must be

  • Protein and Ligand Preparation: Parameters, Protocols, and Influence on Virtual Screening Enrichments

    J Comput Aided Mol Des design 27 (3), 221-234

    Widely Cited

    Structure-based virtual screening plays an important role in drug discovery and complements other screening approaches. In general, protein crystal structures are prepared prior to docking in order to add hydrogen atoms, optimize hydrogen bonds, remove atomic clashes, and perform other operations that are not part of the x-ray crystal structure refinement process. In addition, ligands

  • Structure-Based Virtual Screening of MT2 Melatonin Receptor: Influence of Template Choice and Structural Refinement

    J. Chem. Inf. Model. 2013, 53, 4, 821–835

    Developing GPCR homology models for structure-based virtual screening requires the choice of a suitable template and refinement of binding site residues. We explored this systematically for the MT2 melatonin receptor, with the aim to build a receptor homology model that is optimized for the enrichment of active melatoninergic ligands. A set of 12 MT2 melatonin receptor models