Conformational determinants of the activity of antiproliferative factor glycopeptide.


:The antiproliferative factor (APF) involved in interstitial cystitis is a glycosylated nonapeptide (TVPAAVVVA) containing a sialylated core 1 α-O-disaccharide linked to the N-terminal threonine. The chemical structure of APF was deduced using spectroscopic techniques and confirmed using total synthesis. The synthetic APF provided a platform to study amino acid modifications and their effect on APF activity, based on which a structure-activity relationship (SAR) for APF activity was previously proposed. However, this SAR model could not explain the change in activity associated with minor alterations in the peptide sequence. Presented is computational analysis of 14 APF derivatives to identify structural trends from which a more detailed SAR is obtained. The APF activity is found to be dictated by the close interplay between carbohydrate-peptide and peptide-peptide interactions. The former involves hydrogen bond and hydrophobic interactions, and the latter is dominated by hydrophobic interactions. The highly flexible hydrophobic peptide adopts collapsed conformations separated by low energy barriers. APF activity correlates with hydrophobic clustering associated with amino acids 4A, 6V, and 8V. Peptide conformations are highly sensitive to single point mutations, which explain the experimental trends. The presented SAR will act as a guide for lead optimization of more potent APF analogues of potential therapeutic utility.


J Chem Inf Model


Mallajosyula SS,Adams KM,Barchi JJ,MacKerell AD




Has Abstract


2013-05-24 00:00:00












  • OPUS-Rota3: Improving Protein Side-Chain Modeling by Deep Neural Networks and Ensemble Methods.

    abstract::Side-chain modeling is critical for protein structure prediction since the uniqueness of the protein structure is largely determined by its side-chain packing conformation. In this paper, differing from most approaches that rely on rotamer library sampling, we first propose a novel side-chain rotamer prediction method...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章


    authors: Xu G,Wang Q,Ma J

    更新日期:2020-12-28 00:00:00

  • Characterization of Hydration Properties in Structural Ensembles of Biomolecules.

    abstract::Solute-solvent interactions are critical for biomolecular stability and recognition. Explicit solvent molecular dynamics (MD) simulations are routinely used to probe such interactions. However, detailed analyses and interpretation of the hydration patterns seen in MD simulations can be both complex and time-consuming....

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章


    authors: Pradhan MR,Nguyen MN,Kannan S,Fox SJ,Kwoh CK,Lane DP,Verma CS

    更新日期:2019-07-22 00:00:00

  • Support vector regression scoring of receptor-ligand complexes for rank-ordering and virtual screening of chemical libraries.

    abstract::The community structure-activity resource (CSAR) data sets are used to develop and test a support vector machine-based scoring function in regression mode (SVR). Two scoring functions (SVR-KB and SVR-EP) are derived with the objective of reproducing the trend of the experimental binding affinities provided within the ...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章


    authors: Li L,Wang B,Meroueh SO

    更新日期:2011-09-26 00:00:00

  • Scaffold topologies. 1. Exhaustive enumeration up to eight rings.

    abstract::Mapping the chemical space of small organic molecules is approached from a theoretical graph theory viewpoint, in an effort to begin the systematic exploration of molecular topologies. We present an algorithm for exhaustive generation of scaffold topologies with up to eight rings and an efficient comparison method for...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章


    authors: Pollock SN,Coutsias EA,Wester MJ,Oprea TI

    更新日期:2008-07-01 00:00:00

  • Homology model-guided 3D-QSAR studies of HIV-1 integrase inhibitors.

    abstract::In the present study, we report the exploration of binding modes of potent HIV-1 integrase (IN) inhibitors MK-0518 (raltegravir) and GS-9137 (elvitegravir) as well as chalcone and related amide IN inhibitors we recently synthesized and the development of 3D-QSAR models for integrase inhibition. Homology models of DNA-...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章


    authors: Sharma H,Cheng X,Buolamwini JK

    更新日期:2012-02-27 00:00:00

  • Open Source Bayesian Models. 1. Application to ADME/Tox and Drug Discovery Datasets.

    abstract::On the order of hundreds of absorption, distribution, metabolism, excretion, and toxicity (ADME/Tox) models have been described in the literature in the past decade which are more often than not inaccessible to anyone but their authors. Public accessibility is also an issue with computational models for bioactivity, a...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章


    authors: Clark AM,Dole K,Coulon-Spektor A,McNutt A,Grass G,Freundlich JS,Reynolds RC,Ekins S

    更新日期:2015-06-22 00:00:00

  • Computational and conformational evaluation of FTase alternative substrates: insight into a novel enzyme binding pocket.

    abstract::Protein farnesyltransferase (FTase) is an important anticancer drug target. In an effort to develop isoprenoid diphosphate-based FTase inhibitors, striking variations have been observed in the ability of conservatively modified analogues to bind to the enzyme. For example, 2Z-GGPP is an alternative substrate with high...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章


    authors: Henriksen BS,Zahn TJ,Evanseck JD,Firestine SM,Gibbs RA

    更新日期:2005-07-01 00:00:00

  • Reaction site mapping of xenobiotic biotransformations.

    abstract::Predictive metabolism methods can be used in drug discovery projects to enhance the understanding of structure-metabolism relationships. The present study uses data mining methods to exploit biotransformation data that have been recorded in the MDL Metabolite database. Reacting center fingerprints were derived from a ...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章


    authors: Boyer S,Arnby CH,Carlsson L,Smith J,Stein V,Glen RC

    更新日期:2007-03-01 00:00:00

  • In silico renal clearance model using classical Volsurf approach.

    abstract::A data set of 130 diverse compounds containing both central nervous system (CNS) and non-CNS drugs was used to generate a renal clearance model using a classical Volsurf approach. Percentage renal clearance data was used as a biological input. The score plots obtained from principal component analysis and partial leas...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章


    authors: Doddareddy MR,Cho YS,Koh HY,Kim DH,Pae AN

    更新日期:2006-05-01 00:00:00

  • Pharmer: efficient and exact pharmacophore search.

    abstract::Pharmacophore search is a key component of many drug discovery efforts. Pharmer is a new computational approach to pharmacophore search that scales with the breadth and complexity of the query, not the size of the compound library being screened. Two novel methods for organizing pharmacophore data, the Pharmer KDB-tre...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章


    authors: Koes DR,Camacho CJ

    更新日期:2011-06-27 00:00:00

  • Molecular Dynamics Simulations of Supramolecular Anticancer Nanotubes.

    abstract::We report here on long-time all-atomistic molecular dynamics simulations of functional supramolecular nanotubes composed by the self-assembly of peptide-drug amphiphiles (DAs). These DAs have been shown to possess an inherently high drug loading of the hydrophobic anticancer drug camptothecin. We probe the self-assemb...

    journal_title:Journal of chemical information and modeling

    pub_type: 信件


    authors: Kang M,Chakraborty K,Loverde SM

    更新日期:2018-06-25 00:00:00

  • Relationships between Molecular Complexity, Biological Activity, and Structural Diversity.

    abstract::Following the theoretical model by Hann et al. moderately complex structures are preferable lead compounds since they lead to specific binding events involving the complete ligand molecule. To make this concept usable in practice for library design, we studied several complexity measures on the biological activity of ...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章


    authors: Schuffenhauer A,Brown N,Selzer P,Ertl P,Jacoby E

    更新日期:2006-03-01 00:00:00

  • Random Forest Refinement of Pairwise Potentials for Protein-Ligand Decoy Detection.

    abstract::An accurate scoring function is expected to correctly select the most stable structure from a set of pose candidates. One can hypothesize that a scoring function's ability to identify the most stable structure might be improved by emphasizing the most relevant atom pairwise interactions. However, it is hard to evaluat...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章


    authors: Pei J,Zheng Z,Kim H,Song LF,Walworth S,Merz MR,Merz KM Jr

    更新日期:2019-07-22 00:00:00

  • Comments on the article "Evaluation of pK(a) estimation methods on 211 druglike compounds".

    abstract::The recent article "Evaluation of pK(a) Estimation Methods on 211 Druglike Compounds" ( Manchester, J.; et al. J. Chem Inf. Model. 2010, 50, 565-571 ) reports poor results for the program Epik. Here, we highlight likely sources for the poor performance and describe work done to improve the performance. Running Epik in...

    journal_title:Journal of chemical information and modeling

    pub_type: 评论,杂志文章


    authors: Shelley JC,Calkins D,Sullivan AP

    更新日期:2011-01-24 00:00:00

  • Ranking Reversible Covalent Drugs: From Free Energy Perturbation to Fragment Docking.

    abstract::Reversible covalent inhibitors have drawn increasing attention in drug design, as they are likely more potent than noncovalent inhibitors and less toxic than covalent inhibitors. Despite those advantages, the computational prediction of reversible covalent binding presents a formidable challenge because the binding pr...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章


    authors: Zhang H,Jiang W,Chatterjee P,Luo Y

    更新日期:2019-05-28 00:00:00

  • Exploring Alternative Strategies for the Identification of Potent Compounds Using Support Vector Machine and Regression Modeling.

    abstract::Support vector regression (SVR) is a premier approach for the prediction of compound potency. Given the conceptual link between support vector machine (SVM) and SVR modeling, SVR is capable of accounting for continuous and discontinuous structure-activity relationships (SARs) in potency prediction, which further exten...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章


    authors: Miyao T,Funatsu K,Bajorath J

    更新日期:2019-03-25 00:00:00

  • GPCR-Bench: A Benchmarking Set and Practitioners' Guide for G Protein-Coupled Receptor Docking.

    abstract::Virtual screening is routinely used to discover new ligands and in particular new ligand chemotypes for G protein-coupled receptors (GPCRs). To prepare for a virtual screen, we often tailor a docking protocol that will enable us to select the best candidates for further screening. To aid this, we created GPCR-Bench, a...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章


    authors: Weiss DR,Bortolato A,Tehan B,Mason JS

    更新日期:2016-04-25 00:00:00

  • PyCGTOOL: Automated Generation of Coarse-Grained Molecular Dynamics Models from Atomistic Trajectories.

    abstract::Development of coarse-grained (CG) molecular dynamics models is often a laborious process which commonly relies upon approximations to similar models, rather than systematic parametrization. PyCGTOOL automates much of the construction of CG models via calculation of both equilibrium values and force constants of inter...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章


    authors: Graham JA,Essex JW,Khalid S

    更新日期:2017-04-24 00:00:00

  • Dependence of QSAR models on the selection of trial descriptor sets: a demonstration using nanotoxicity endpoints of decorated nanotubes.

    abstract::Little attention has been given to the selection of trial descriptor sets when designing a QSAR analysis even though a great number of descriptor classes, and often a greater number of descriptors within a given class, are now available. This paper reports an effort to explore interrelationships between QSAR models an...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章


    authors: Shao CY,Chen SZ,Su BH,Tseng YJ,Esposito EX,Hopfinger AJ

    更新日期:2013-01-28 00:00:00

  • How Well Does the Extended Linear Interaction Energy Method Perform in Accurate Binding Free Energy Calculations?

    abstract::With continually increased computer power, molecular mechanics force field-based approaches, such as the endpoint methods of molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) and molecular mechanics generalized Born surface area (MM-GBSA), have been routinely applied in both drug lead identification and opt...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章


    authors: Hao D,He X,Ji B,Zhang S,Wang J

    更新日期:2020-12-28 00:00:00

  • Gas-phase and solution conformations of selected dimeric structural units of heparin.

    abstract::The molecular structure of four dimeric units (D-E, E-F, F-G, and G-H) of the DEFGH structural unit of heparin, their anionic forms, and their sodium salts have been studied using the B3LYP/6-31+G(d) method. The optimized geometries indicate that the most stable structure of these dimeric units in neutral state is sta...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章


    authors: Remko M,von der Lieth CW

    更新日期:2006-07-01 00:00:00

  • Loop Grafting between Similar Local Environments for Fc-Silent Antibodies.

    abstract::Reduction of the affinity of the fragment crystallizable (Fc) region with immune receptors by substitution of one or a few amino acids, known as Fc-silencing, is an established approach to reduce the immune effector functions of monoclonal antibody therapeutics. This approach to Fc-silencing, however, is problematic a...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章


    authors: Lešnik S,Hodošček M,Podobnik B,Konc J

    更新日期:2020-11-23 00:00:00

  • Fragment-Based Computational Method for Designing GPCR Ligands.

    abstract::G protein-coupled receptors (GPCRs) are the largest family of cell surface receptors, which is arguably the most important family of drug target. With the technology breakthroughs in X-ray crystallography and cryo-electron microscopy, more than 300 GPCR-ligand complex structures have been publicly reported since 2007,...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章


    authors: Li Y,Sun Y,Song Y,Dai D,Zhao Z,Zhang Q,Zhong W,Hu LA,Ma Y,Li X,Wang R

    更新日期:2020-09-28 00:00:00

  • Molecular modeling of DNA cross-linking analogues based on the azinomycin scaffold.

    abstract::In this work, we present molecular modeling studies carried out using six DNA sequences and six azinomycin analogues, including the naturally occurring compound azinomycin B, selected on the basis of known cell cytotoxicity and structural analogies (epoxide and aziridine alkylating moieties). Among several computation...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章


    authors: Alcaro S,Ortuso F,Coleman RS

    更新日期:2005-05-01 00:00:00

  • GalaxyGPCRloop: Template-Based and Ab Initio Structure Sampling of the Extracellular Loops of G-Protein-Coupled Receptors.

    abstract::The second extracellular loops (ECL2s) of G-protein-coupled receptors (GPCRs) are often involved in GPCR functions, and their structures have important implications in drug discovery. However, structure prediction of ECL2 is difficult because of its long length and the structural diversity among different GPCRs. In th...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章


    authors: Won J,Lee GR,Park H,Seok C

    更新日期:2018-06-25 00:00:00

  • Comparative Binding Analysis of N-Acetylneuraminic Acid in Bovine Serum Albumin and Human α-1 Acid Glycoprotein.

    abstract::The present study focuses on the determination of the biologically significant N-acetylneuraminic acid (NANA) drug binding interaction mechanism between bovine serum albumin (BSA) and human α-1 acid glycoprotein (HAG) using various optical spectroscopy and computational methods. The steady state fluorescence spectrosc...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章


    authors: Karthikeyan S,Bharanidharan G,Ragavan S,Kandasamy S,Chinnathambi S,Udayakumar K,Mangaiyarkarasi R,Sundaramoorthy A,Aruna P,Ganesan S

    更新日期:2019-01-28 00:00:00

  • RED: a set of molecular descriptors based on Renyi entropy.

    abstract::New molecular descriptors, RED (Renyi entropy descriptors), based on the generalized entropies introduced by Renyi are presented. Topological descriptors based on molecular features have proven to be useful for describing molecular profiles. Renyi entropy is used as a variability measure to contract a feature-pair dis...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章


    authors: Delgado-Soler L,Toral R,Tomás MS,Rubio-Martinez J

    更新日期:2009-11-01 00:00:00

  • Flux (2): comparison of molecular mutation and crossover operators for ligand-based de novo design.

    abstract::We implemented a fragment-based de novo design algorithm for a population-based optimization of molecular structures. The concept is grounded on an evolution strategy with mutation and crossover operators for structure breeding. Molecular building blocks were obtained from the pseudo-retrosynthesis of a collection of ...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章


    authors: Fechner U,Schneider G

    更新日期:2007-03-01 00:00:00

  • Study of chromatographic retention of natural terpenoids by chemoinformatic tools.

    abstract::The study of chromatographic retention of natural products can be used to increase their identification speed in complex biological matrices. In this work, six variables were used to study the retention behavior in reversed phase liquid chromatography of 39 sesquiterpene lactones (SL) from an in-house database using c...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章


    authors: Oliveira TB,Gobbo-Neto L,Schmidt TJ,Da Costa FB

    更新日期:2015-01-26 00:00:00

  • Structure-Based Discovery of 1H-Indazole-3-carboxamides as a Novel Structural Class of Human GSK-3 Inhibitors.

    abstract::An in silico screening procedure was performed to select new inhibitors of glycogen synthase kinase 3β (GSK-3β), a serine/threonine protein kinase that in the last two decades has emerged as a key target in drug discovery, having been implicated in multiple cellular processes and linked with the pathogenesis of severa...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章


    authors: Ombrato R,Cazzolla N,Mancini F,Mangano G

    更新日期:2015-12-28 00:00:00