Abstract：
: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.
journal_name
J Chem Inf Modeljournal_title
Journal of chemical information and modelingauthors
Mallajosyula SS,Adams KM,Barchi JJ,MacKerell ADdoi
10.1021/ci400147ssubject
Has Abstractpub_date
2013-05-24 00:00:00pages
1127-37issue
5eissn
1549-9596issn
1549-960Xjournal_volume
53pub_type
杂志文章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
doi：10.1021/ci3005308
更新日期：2013-01-28 00:00:00
abstract：:Peptides that bind to ion channels have attracted much interest as potential lead molecules for the development of new drugs and insecticides. However, the structure determination of large peptide-channel complexes using experimental methods is challenging. Thus structural models are often derived from combining exper...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.5b00529
更新日期：2016-01-25 00:00:00
abstract：:The SZMAP method computes binding free energies and the corresponding thermodynamic components for water molecules in the binding site of a protein structure [ SZMAP, 1.0.0 ; OpenEye Scientific Software Inc. : Santa Fe, NM, USA , 2011 ]. In this work, the ability of SZMAP to predict water structure and thermodynamic s...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci500746d
更新日期：2015-08-24 00:00:00
abstract：:Membrane-bound protein receptors are a primary biological drug target, but the computational analysis of membrane proteins has been limited. In order to improve molecular mechanics Poisson-Boltzmann surface area (MMPBSA) binding free energy calculations for membrane protein-ligand systems, we have optimized a new hete...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00363
更新日期：2019-06-24 00:00:00
abstract：:Due to the recent availability of high quality small molecule databases, such as ZINC and PubChem,1,2 virtual screening is playing an even more important role in identifying biologically relevant molecules in drug discovery campaigns. The success of pharmacophore-based virtual screening (PBVS) relies largely on the ac...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci700089w
更新日期：2007-07-01 00:00:00
abstract：:Advances in computer-aided translation technology have made tremendous progress in accuracy in the past few years. Chemical Abstracts Service of the American Chemical Society summarizes scientific works from more than 50 languages and allows the users to search papers in nine selected languages. Currently, only the ab...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.0c00274
更新日期：2020-07-27 00:00:00
abstract：:Here, a method is described for easily building three-carbon nanotube junctions. It allows the geometry to be found and bond connectivity of C(3) symmetric nanotube junctions to be established. Such junctions may present a variable degree of pyramidalization and are composed of three identical carbon nanotubes with ar...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci200056p
更新日期：2011-06-27 00:00:00
abstract：:In this work, we report an ab initio investigation based on density functional theory calculations within van der Waals D3 corrections to investigate the adsorption properties and activation of CO2 on transition-metal (TM) 13-atom clusters (TM = Ru, Rh, Pd, Ag), which is a key step for the development of subnano catal...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00792
更新日期：2020-02-24 00:00:00
abstract：:Many of the conventional similarity methods assume that molecular fragments that do not relate to biological activity carry the same weight as the important ones. One possible approach to this problem is to use the Bayesian inference network (BIN), which models molecules and reference structures as probabilistic infer...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci100232h
更新日期：2011-01-24 00:00:00
abstract：:DiSCuS, a "Database System for Compound Selection", has been developed. The primary goal of DiSCuS is to aid researchers in the steps subsequent to generating high-throughput virtual screening (HTVS) results, such as selection of compounds for further study, purchase, or synthesis. To do so, DiSCuS provides (1) a stor...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci400587f
更新日期：2014-01-27 00:00:00
abstract：:Computer programs for structure diagram generation (SDG) are indispensable cheminformatic tools that translate one- or three-dimensional (1D or 3D) chemical structure data stored in electronic formats to human-readable 2D depictions. Although many such programs are known, only a moderate part of chemical space can be ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.6b00391
更新日期：2016-12-27 00:00:00
abstract：:Optimization of ligand binding affinity to the target protein of interest is a primary objective in small-molecule drug discovery. Until now, the prediction of binding affinities by computational methods has not been widely applied in the drug discovery process, mainly because of its lack of accuracy and reproducibili...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.6b00780
更新日期：2017-04-24 00:00:00
abstract：:One of the largest commercial applications of enzymes and surfactants is as main components in modern detergents. The high concentration of surfactant compounds usually present in detergents can, however, negatively affect the enzymatic activity. To remedy this drawback, it is of great importance to characterize the i...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.8b00857
更新日期：2019-05-28 00:00:00
abstract：:The hepatitis C virus (HCV) NS5B RNA-dependent RNA polymerase (RdRP) is a crucial and unique component of the HCV RNA replication machinery and a validated target for drug discovery. Multiple crystal structures of NS5B inhibitor complexes have facilitated the identification of novel compound scaffolds through in silic...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci400644r
更新日期：2014-02-24 00:00:00
abstract：:A comprehensive safety evaluation of chemicals should require toxicity assessment in both the aquatic and terrestrial test species. Due to the application practices and nature of chemical pesticides, the avian toxicity testing is considered as an essential requirement in the risk assessment process. In this study, tre...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.5b00139
更新日期：2015-07-27 00:00:00
abstract：:Several hypotheses to elucidate the linkage isomer preference of the thiocyanate (SCN(-)) ion have been offered. For complexes with small coordination numbers (i.e., 1 and 2) and groups 11 (Cu-triad) and 12 (Zn-triad) metals, different levels of theory and a variety of basis sets have been employed to study linkage is...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci050050t
更新日期：2005-07-01 00:00:00
abstract：:Sixteen FDA-approved drugs were investigated to elucidate their mechanisms of action (MOAs) and clinical functions by pathway analysis based on retrieved drug targets interacting with or affected by the investigated drugs. Protein and gene targets and associated pathways were obtained by data-mining of public database...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci4005354
更新日期：2014-02-24 00:00:00
abstract：:Model lipid membranes made from binary mixtures of dimyristoylphosphatidylcholine/dipalmitoylphosphatidylcholine (DMPC/DPPC) and dimyristoylphosphatidylcholine/cholesterol (DMPC/Chol) exhibit coexistence of diverse lipid phases at appropriate temperature and composition. Since lipids in different phases show different...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci0501793
更新日期：2005-11-01 00:00:00
abstract：:Reaction classification has important applications, and many approaches to classification have been applied. Our own algorithm tests all maximum common substructures (MCS) between all reactant and product molecules in order to find an atom mapping containing the minimum chemical distance (MCD). Recent publications hav...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci400442f
更新日期：2013-11-25 00:00:00
abstract：:Inhibition of plasmin has been found to effectively reduce fibrinolysis and to avoid hemorrhage. This can be achieved by addressing its kringle 1 domain with the known drug and lysine analogue tranexamic acid. Guided by shape similarities toward a previously discovered lead compound, 5-(4-piperidyl)isoxazol-3-ol, a se...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.7b00255
更新日期：2017-07-24 00:00:00
abstract：:To promote more productive combinatorial endeavors, the Diversity Space methodology introduced here enables similarity comparisons at the library level. Particularly at an early screening stage, when little or no information is available regarding the pharmacophoric entities necessary for binding, it is more efficient...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci060066z
更新日期：2006-07-01 00:00:00
abstract：:The early stages of drug discovery rely on hit-to-lead programs, where initial hits undergo partial optimization to improve binding affinities for their biological target. This is an expensive and time-consuming process, requiring multiple iterations of trial and error designs, an ideal scenario for applying computer ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00938
更新日期：2020-03-23 00:00:00
abstract：:While critically reviewing the current status of what is known about C28H14 and C30H14 benzenoid isomers, which are ubiquitous pyrolytic constituents, some new insights will be presented. Representative isomers belonging to these benzenoid hydrocarbons are at the crossroads to homologous series that extend to infinite...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci050298i
更新日期：2006-03-01 00:00:00
abstract：:Template CoMFA, a novel alignment methodology for training or test set structures in 3D-QSAR, is introduced. Its two most significant advantages are its complete automation and its ability to derive a single combined model from multiple structural series affecting a biological target. Its only two inputs are one or mo...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci400696v
更新日期：2014-02-24 00:00:00
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
doi：10.1021/acs.jcim.5b00143
更新日期：2015-06-22 00:00:00
abstract：:Structure-based virtual screening relies on classical scoring functions that often fail to reliably discriminate binders from nonbinders. In this work, we present a high-throughput protein-ligand complex molecular dynamics (MD) simulation that uses the output from AutoDock Vina to improve docking results in distinguis...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.0c00057
更新日期：2020-04-27 00:00:00
abstract：:We introduce SARANEA, an open-source Java application for interactive exploration of structure-activity relationship (SAR) and structure-selectivity relationship (SSR) information in compound sets of any source. SARANEA integrates various SAR and SSR analysis functions and utilizes a network-like similarity graph data...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci900416a
更新日期：2010-01-01 00:00:00
abstract：:Machine learning (ML) algorithms are gaining importance in the processing of chemical information and modeling of chemical reactivity problems. In this work, we have developed a perturbation-theory and machine learning (PTML) model combining perturbation theory (PT) and ML algorithms for predicting the yield of a give...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.8b00286
更新日期：2018-07-23 00:00:00
abstract：:One tactic for cysteine protease inhibition is to form a covalent bond between an electrophilic atom of the inhibitor and the thiol of the catalytic cysteine. In this study, we evaluate the reaction free energy obtained from a hybrid quantum mechanical/molecular mechanical (QM/MM) free energy profile as a predictor of...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00847
更新日期：2020-02-24 00:00:00
abstract：:The binding affinity and relative maximal efficacy of human A3 adenosine receptor (AR) agonists were each subjected to ligand-based three-dimensional quantitative structure-activity relationship analysis. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) used a...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci600501z
更新日期：2007-05-01 00:00:00
