Abstract:
:Resistance remains a major issue with regards to HIV-1 protease, despite the availability of numerous HIV-1 protease inhibitors and copious amounts of structural and binding data. In an effort to improve our understanding of how HIV-1 protease is able to "outsmart" new drugs, we have investigated the flexibility of HIV-1 protease and in particular how it adapts to different structural stresses. Our analysis has highlighted the effects of space group on the variability between structures of HIV-1 protease and suggests that consideration of multiple structures and appropriate consideration of different conformations of the Ile50 residue is necessary in any structural analysis. Calculation of the root-mean-square deviation on a per-residue basis has been used to identify 'natural variation', while mutational and ligand analyses have been carried out to identify the effect on structure as a result of specific stresses. It was observed that mutations readily cause changes to occur at sites both close to and distant from a mutation site, with changes more likely to occur at residues that are sites of other major mutations. It is also revealed that HIV-1 protease adaption is dependent on the type and the structure of any bound ligand. Identification of the specific changes that occur due to these stresses will aid in the understanding of resistance and also aid in the design of new drugs.
journal_name
J Chem Inf Modeljournal_title
Journal of chemical information and modelingauthors
Oehme DP,Wilson DJ,Brownlee RTdoi
10.1021/ci2000677subject
Has Abstractpub_date
2011-05-23 00:00:00pages
1064-73issue
5eissn
1549-9596issn
1549-960Xjournal_volume
51pub_type
杂志文章abstract::We introduce the statistics behind a novel type of SAR analysis named "nonadditivity analysis". On the basis of all pairs of matched pairs within a given data set, the approach analyzes whether the same transformations between related molecules have the same effect, i.e., whether they are additive. Assuming that the e...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.9b00631
更新日期:2019-09-23 00:00:00
abstract::Estrogens exert important physiological effects through the modulation of two human estrogen receptor (hER) subtypes, alpha (hERalpha) and beta (hERbeta). Because the levels and relative proportion of hERalpha and hERbeta differ significantly in different target cells, selective hER ligands could target specific tissu...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci8002182
更新日期:2008-11-01 00:00:00
abstract::The configuring of a radial basis function network (RBFN) consists of selecting the network parameters (centers and widths in RBF units and weights between the hidden and output layers) and network architecture. The issues of suboptimum and overfitting, however, often occur in RBFN configuring. This paper presented a ...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci600218d
更新日期:2006-11-01 00:00:00
abstract::When both the difference between two quantities and their individual values can be measured or computationally predicted, multiple quantities can be determined from the measurements or predictions of select individual quantities and select pairwise differences. These measurements and predictions form a network connect...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.9b00528
更新日期:2019-11-25 00:00:00
abstract::As a result of the widespread industrial use of polychlorinated hydrocarbons, they have accumulated in nearly all types of environmental compartments, especially in aquatic systems. Particularly, chloroaromatics are among the most undesirable industrial effluents because of their persistence and toxicity. To predict c...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci0501342
更新日期:2005-07-01 00:00:00
abstract::A kinetic, reactivity-binding model has been proposed to predict the regioselectivity of substrates meditated by the CYP1A2 enzyme, which is responsible for the metabolism of planar-conjugated compounds such as caffeine. This model consists of a docking simulation for binding energy and a semiempirical molecular orbit...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci800001m
更新日期:2008-05-01 00:00:00
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
doi:10.1021/ci600376q
更新日期:2007-03-01 00:00:00
abstract::Grass weed populations resistant to acetyl-CoA carboxylase-inhibiting (ACCase; EC 6.4.1.2) herbicides represent a major problem for the sustainable development of modern agriculture. In the present study, extensive computational simulations, including homology modeling, molecular dynamics (MD) simulations, and molecul...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci900174d
更新日期:2009-08-01 00:00:00
abstract::CYP19A1, also known as aromatase or estrogen synthetase, is the rate-limiting enzyme in the biosynthesis of estrogens from their corresponding androgens. Several clinically used breast cancer therapies target aromatase. In this work, explicitly solvated all-atom molecular dynamics simulations of aromatase with a model...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci400225w
更新日期:2013-08-26 00:00:00
abstract::The interaction between small molecules and proteins is one of the major concerns for structure-based drug design because the principles of protein-ligand interactions and molecular recognition are not thoroughly understood. Fortunately, the analysis of protein-ligand complexes in the Protein Data Bank (PDB) enables u...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci100386y
更新日期:2011-04-25 00:00:00
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
doi:10.1021/acs.jcim.8b00453
更新日期:2019-07-22 00:00:00
abstract::Mass spectrometric data are copious and generate a processing burden that is best dealt with programmatically. PythoMS is a collection of tools based on the Python programming language that assist researchers in creating figures and video output that is informative, clear, and visually compelling. The PythoMS framewor...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.9b00055
更新日期:2019-04-22 00:00:00
abstract::Deep learning has demonstrated significant potential in advancing state of the art in many problem domains, especially those benefiting from automated feature extraction. Yet, the methodology has seen limited adoption in the field of ligand-based virtual screening (LBVS) as traditional approaches typically require lar...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.0c00622
更新日期:2020-10-26 00:00:00
abstract::Given the need for modern researchers to produce open, reproducible scientific output, the lack of standards and best practices for sharing data and workflows used to produce and analyze molecular dynamics (MD) simulations has become an important issue in the field. There are now multiple well-established packages to ...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.9b00665
更新日期:2019-10-28 00:00:00
abstract::Due to the importance of hot-spots (HS) detection and the efficiency of computational methodologies, several HS detecting approaches have been developed. The current paper presents new models to predict HS for protein-protein and protein-nucleic acid interactions with better statistics compared with the ones currently...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci500760m
更新日期:2015-05-26 00:00:00
abstract::Reversible and irreversible covalent ligands are advanced cysteine protease inhibitors in the drug development pipeline. K777 is an irreversible inhibitor of cruzain, a necessary enzyme for the survival of the Trypanosoma cruzi (T. cruzi) parasite, the causative agent of Chagas disease. Despite their importance, irrev...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.9b01138
更新日期:2020-03-23 00:00:00
abstract::A comprehensive data set of aligned ligands with highly similar binding pockets from the Protein Data Bank has been built. Based on this data set, a scoring function for recognizing good alignment poses for small molecules has been developed. This function is based on atoms and hydrogen-bond projected features. The co...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci100227h
更新日期:2010-09-27 00:00:00
abstract::Naturally occurring anticancer compounds represent about half of the chemotherapeutic drugs which have been put in the market against cancer until date. Computer-based or in silico virtual screening methods are often used in lead/hit discovery protocols. In this study, the "drug-likeness" of ~400 compounds from Africa...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci5003697
更新日期:2014-09-22 00:00:00
abstract::Three-dimensional protein structures are a key requisite for structure-based drug discovery. For many highly relevant targets, medicinal chemists are confronted with large numbers of target structures in their apo-forms or in complex with a wealth of different ligands. To exploit the full potential of such structure e...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.0c00051
更新日期:2020-04-27 00:00:00
abstract::G-protein coupled receptors (GPCRs) are highly relevant drug targets. Four GPCRs with known crystal structure were analyzed with docking (AutoDock4) and postdocking (MM-PBSA) in order to evaluate the ability to recognize known antagonists from a larger database of molecular decoys and to predict correct binding modes....
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci4000745
更新日期:2013-04-22 00:00:00
abstract::A new web portal for the CHARMM macromolecular modeling package, CHARMMing (CHARMM interface and graphics, http://www.charmming.org), is presented. This tool provides a user-friendly interface for the preparation, submission, monitoring, and visualization of molecular simulations (i.e., energy minimization, solvation,...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci800133b
更新日期:2008-09-01 00:00:00
abstract::Cyanobacterial fructose-1,6-/sedoheptulose-1,7-bisphoshatase (cy-FBP/SBPase) is a potential enzymatic target for screening of novel inhibitors that can combat harmful algal blooms. In the present study, we targeted the substrate binding pocket of cy-FBP/SBPase. A series of novel hit compounds from the SPECs database w...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci4007529
更新日期:2014-03-24 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::Metabolic stability is an important property of drug molecules that should-optimally-be taken into account early on in the drug design process. Along with numerous medium- or high-throughput assays being implemented in early drug discovery, a prediction tool for this property could be of high value. However, metabolic...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci700142c
更新日期:2008-04-01 00:00:00
abstract::The importance of thorough analyses of the secondary structures in proteins as basic structural units cannot be overemphasized. Although recent computational methods have achieved reasonably high accuracy for predicting secondary structures from amino acid sequences, a simple and fundamental empirical approach to char...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci900452z
更新日期:2010-04-26 00:00:00
abstract::Herein we present the VMD Store, an open-source VMD plugin that simplifies the way that users browse, discover, install, update, and uninstall extensions for the Visual Molecular Dynamics (VMD) software. The VMD Store obtains data about all the indexed VMD extensions hosted on GitHub and presents a one-click mechanism...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.9b00739
更新日期:2019-11-25 00:00:00
abstract::In this DFT study, activities of 11 different N2O4, N2O3, and NO2 core containing Zr(IV) complexes, 4,13-diaza-18-crown-6 (I'N2O4), 1,4,10-trioxa-7,13-diazacyclopentadecane (I'N2O3), and 2-(2-methoxy)ethanol (I'NO2), respectively, and their analogues in peptide hydrolysis have been investigated. Based on the experimen...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.6b00781
更新日期:2017-05-22 00:00:00
abstract::Membrane fusion, a key step in the early stages of virus propagation, allows the release of the viral genome in the host cell cytoplasm. The process is initiated by fusion peptides that are small, hydrophobic components of viral membrane-embedded glycoproteins and are typically conserved within virus families. Here, w...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.0c01231
更新日期:2021-01-25 00:00:00
abstract::As computational drug design becomes increasingly reliant on virtual screening and on high-throughput 3D modeling, the need for fast, robust, and reliable methods for sampling molecular conformations has become greater than ever. Furthermore, chemical novelty is at a premium, forcing medicinal chemists to explore more...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci900238a
更新日期:2009-10-01 00:00:00
abstract::A compound's synthetic accessibility (SA) is an important aspect of drug design, since in some cases computer-designed compounds cannot be synthesized. There have been several reports on SA prediction, most of which have focused on the difficulties of synthetic reactions based on retro-synthesis analyses, reaction dat...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci500568d
更新日期:2014-12-22 00:00:00