Abstract：
:Antimicrobial peptides (AMPs) have emerged as promising therapeutic alternatives to fight against the diverse infections caused by different pathogenic microorganisms. In this context, theoretical approaches in bioinformatics have paved the way toward the creation of several in silico models capable of predicting antimicrobial activities of peptides. All current models have several significant handicaps, which prevent the efficient search for highly active AMPs. Here, we introduce the first multitarget (mt) chemo-bioinformatic model devoted to performing alignment-free prediction of antibacterial activity of peptides against multiple Gram-positive bacterial strains. The model was constructed from a data set containing 2488 cases of AMPs sequences assayed against at least 1 out of 50 Gram-positive bacterial strains. This mt-chemo-bioinformatic model displayed percentages of correct classification higher than 90.00% in both training and prediction (test) sets. For the first time, two computational approaches derived from basic concepts in genetics and molecular biology were applied, allowing the calculations of the relative contributions of any amino acid (in a defined position) to the antibacterial activity of an AMP and depending on the bacterial strain used in the biological assay. The present mt-chemo-bioinformatic model constitutes a powerful tool to enable the discovery of potent and versatile AMPs.
journal_name
J Chem Inf Modeljournal_title
Journal of chemical information and modelingauthors
Speck-Planche A,Kleandrova VV,Ruso JM,Cordeiro MNdoi
10.1021/acs.jcim.5b00630subject
Has Abstractpub_date
2016-03-28 00:00:00pages
588-98issue
3eissn
1549-9596issn
1549-960Xjournal_volume
56pub_type
杂志文章abstract：:The balance between structural stability and functional plasticity in proteins that share common three-dimensional folds is the key factor that drives protein evolvability. The ability to distinguish the parts of homologous proteins that underlie common structural organization patterns from the parts acting as regulat...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.6b00504
更新日期：2017-04-24 00:00:00
abstract：:The causative agent of African sleeping sickness, Trypanosoma brucei , undergoes an unusual mitochondrial RNA editing process that is essential for its survival. RNA editing terminal uridylyl transferase 2 of T. brucei (TbRET2) is an indispensable component of the editosome machinery that performs this editing. TbR...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci3001327
更新日期：2012-05-25 00:00:00
abstract：:There is a renewed interest in computer-aided synthesis planning, where the vast majority of approaches require the application of retrosynthetic reaction templates. Here we introduce RDChiral, an open-source Python wrapper for RDKit designed to provide consistent handling of stereochemical information in applying ret...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00286
更新日期：2019-06-24 00:00:00
abstract：:The possibility of improving the predictive ability of comparative molecular field analysis (CoMFA) by settings optimization has been evaluated to show that CoMFA predictive ability can be improved. Ten different CoMFA settings are evaluated, producing a total of 6120 models. This method has been applied to nine diffe...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci049612j
更新日期：2006-01-01 00:00:00
abstract：:The high-throughput docking protocol called ALTA-VS (anchor-based library tailoring approach for virtual screening) was developed in 2005 for the efficient in silico screening of large libraries of compounds by preselection of only those molecules that have optimal fragments (anchors) for the protein target. Here we p...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.7b00336
更新日期：2017-10-23 00:00:00
abstract：:Binding affinity prediction with implicit solvent models remains a challenge in virtual screening for drug discovery. In order to assess the predictive power of implicit solvent models in docking techniques with Amber scoring, three generalized Born models (GBHCT, GBOBCI, and GBOBCII) available in Dock 6.7 were utiliz...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.6b00418
更新日期：2016-10-24 00:00:00
abstract：:Dual and triple activity-difference (DAD/TAD) maps are tools for the systematic characterization of structure-activity relationships (SAR) of compound data sets screened against two or three targets. DAD and TAD maps are two- and three- dimensional representations of the pairwise activity differences of compound data ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci200281v
更新日期：2011-09-26 00:00:00
abstract：:A major concern of chemogenomics is to associate drug activity with biological variables. Several reports have clustered cell line drug activity profiles as well as drug activity-gene expression correlation profiles and noted that the resulting groupings differ but still reflect mechanism of action. The present paper ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci060073n
更新日期：2007-01-01 00:00:00
abstract：:The Common Instrument Middleware Architecture (CIMA) aims at Grid-enabling a wide range of scientific instruments and sensors to enable easy access to and sharing and storage of data produced by these instruments and sensors. This paper describes the implementation of CIMA applied to the field of single-crystal X-ray ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci050368l
更新日期：2006-05-01 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：:The large volume of protein-ligand structures now available enables innovative and efficient protocols in computational FBDD (Fragment-Based Drug Design) to be proposed based on experimental data. In this work, we build a database of MED-Portions, where a MED-Portion is a new structural object encoding protein-fragmen...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci8003094
更新日期：2009-02-01 00:00:00
abstract：:Protein dynamics play a critical role in ligand binding, and different models have been proposed to explain the relationships between protein motion and molecular recognition. Here, we present a study of ligand-binding processes associated with large conformational changes of a protein to elucidate the critical choice...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.7b00125
更新日期：2017-07-24 00:00:00
abstract：:The viral NS5B RNA-dependent RNA-polymerase (RdRp) is one of the best-studied and promising targets for the development of novel therapeutics against hepatitis C virus (HCV). Allosteric inhibition of this enzyme has emerged as a viable strategy toward blocking replication of viral RNA in cell based systems. Herein, we...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci9004749
更新日期：2010-04-26 00:00:00
abstract：:Databases of small, potentially bioactive molecules are ubiquitous across the industry and academia. Designed such that each unique compound should appear only once, the multiplicity of ways in which many compounds can be represented means that these databases require methods for standardizing the representation of ch...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.0c00232
更新日期：2020-08-24 00:00:00
abstract：:A MMGBSA variant (here referred to as Nwat-MMGBSA), based on the inclusion of a certain number of explicit water molecules (Nwat) during the calculations, has been tested on a set of 20 protein-protein complexes, using the correlation between predicted and experimental binding energy as the evaluation metric. Besides ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.6b00196
更新日期：2016-09-26 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：:The primary goal of ligand-based virtual screening is to identify active compounds consisting of a core scaffold that is not found in the current active compound pool. Scaffold hopping is the term used for this purpose. In the present study, topological representations of pharmacophore features on chemical graphs were...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.0c00098
更新日期：2020-04-27 00:00:00
abstract：:The solvation layer surrounding a protein is clearly an intrinsic part of protein structure-dynamics-function, and our understanding of how the hydration dynamics influences protein function is emerging. We have recently reported simulations indicating a correlation between regional hydration dynamics and the structur...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00009
更新日期：2019-05-28 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：:Development of accurate force field parameters for molecular ions in the context of a polarizable energy function based on the classical Drude oscillator is a crucial step toward an accurate polarizable model for modeling and simulations of biological macromolecules. Toward this goal we have undertaken a hierarchical ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.8b00132
更新日期：2018-05-29 00:00:00
abstract：:An important issue in developing protein-ligand docking methods is how to incorporate receptor flexibility. Consideration of receptor flexibility using an ensemble of precompiled receptor conformations or by employing an effectively enlarged binding pocket has been reported to be useful. However, direct consideration ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci300342z
更新日期：2012-12-21 00:00:00
abstract：:The [H2X2]+ (X = Cl, Br) formula could refer to two possible stable structures, namely, the hydrogen-bonded complex and the three-electron-bonded one. In contrary to the results published by other authors, we claim that for the F-type structures the hydrogen-bonded form is the only possible one and the [HFFH]+ complex...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci600355g
更新日期：2007-05-01 00:00:00
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
doi：10.1021/ci200078f
更新日期：2011-09-26 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：:We present an algorithm, ReFlex3D, for the refinement of flexible molecular alignments based on their three-dimensional shape and electrostatic properties. The algorithm is designed to be used with fast conformer generators to refine an initial overlay between two molecules and thus to obtain improved overlaps as judg...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.7b00618
更新日期：2018-04-23 00:00:00
abstract：:With chemical libraries increasingly containing millions of compounds or more, there is a fast-growing need for computational methods that can rank or prioritize compounds for screening. Machine learning methods have shown considerable promise for this task; indeed, classification methods such as support vector machin...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci9003865
更新日期：2010-05-24 00:00:00
abstract：:The knowledge of the capacity of a data set to be modeled in the first stages of the building of quantitative structure-activity relationship (QSAR) prediction models is an important issue because it might reduce the effort and time necessary to select or reject data sets and in refining the data set's composition. Th...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.8b00188
更新日期：2018-09-24 00:00:00
abstract：:Structure-based computational target prediction methods identify potential targets for a bioactive compound. Methods based on protein-ligand docking so far face many challenges, where the greatest probably is the ranking of true targets in a large data set of protein structures. Currently, no standard data sets for ev...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci500131x
更新日期：2014-08-25 00:00:00
abstract：:In the present work, the Henderson-Hasselbalch (HH) equation has been employed for the development of a tool for the prediction of pH-dependent aqueous solubility of drugs and drug candidates. A new prediction method for the intrinsic solubility was developed, based on artificial neural networks that have been trained...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci600292q
更新日期：2006-11-01 00:00:00
abstract：:We have performed a systematic study of the entropy term in the MM/GBSA (molecular mechanics combined with generalized Born and surface-area solvation) approach to calculate ligand-binding affinities. The entropies are calculated by a normal-mode analysis of harmonic frequencies from minimized snapshots of molecular d...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci3001919
更新日期：2012-08-27 00:00:00
