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-assembly mechanism from random with ∼0.4 μs molecular dynamics simulations. Furthermore, we also computationally characterize the interfacial structure, directionality of π-π stacking, and water dynamics within several peptide-drug nanotubes with diameters consistent with the reported experimental nanotube diameter. Insight gained should inform the future design of these novel anticancer drug delivery systems.
journal_name
J Chem Inf Modeljournal_title
Journal of chemical information and modelingauthors
Kang M,Chakraborty K,Loverde SMdoi
10.1021/acs.jcim.8b00193subject
Has Abstractpub_date
2018-06-25 00:00:00pages
1164-1168issue
6eissn
1549-9596issn
1549-960Xjournal_volume
58pub_type
信件abstract：:Small molecule flexible alignment is a critical component of both ligand- and structure-based methods in computer-aided drug discovery. Despite its importance, the availability of high-quality flexible alignment software packages is limited. Here, we present BCL::MolAlign, a freely available property-based molecular a...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00020
更新日期：2019-02-25 00:00:00
abstract：:In this study, we tried to establish a general scheme to create a model that could predict the affinity of small compounds to their target proteins. This scheme consists of a search for ligand-binding sites on a protein, a generation of bound conformations (poses) of ligands in each of the sites by docking, identifica...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci800313h
更新日期：2009-04-01 00:00:00
abstract：:G-protein-coupled receptors (GPCRs) transmit signals into the cell in response to ligand binding at its extracellular domain, which is characterized by the coupling of agonist-induced receptor conformational change to guanine nucleotide (GDP) exchange with guanosine triphosphate on a heterotrimeric (αβγ) guanine nucle...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.0c00432
更新日期：2020-08-24 00:00:00
abstract：:Universal generative topographic maps (GTMs) provide two-dimensional representations of chemical space selected for their "polypharmacological competence", that is, the ability to simultaneously represent meaningful activity and property landscapes, associated with many distinct targets and properties. Several such GT...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.8b00650
更新日期：2019-01-28 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
abstract：:In this work we present the third generation of FAst MEtabolizer (FAME 3), a collection of extra trees classifiers for the prediction of sites of metabolism (SoMs) in small molecules such as drugs, druglike compounds, natural products, agrochemicals, and cosmetics. FAME 3 was derived from the MetaQSAR database ( Pedre...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00376
更新日期：2019-08-26 00:00:00
abstract：:QSPR studies, using scores of SciTegic's extended connectivity fingerprint as raw descriptors, were extended to the prediction of melting points and aqueous solubility of organic compounds. Robust partial least-squares models were developed that perform as well as the best published QSPR models for structurally divers...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci800024c
更新日期：2008-05-01 00:00:00
abstract：:The applicability and scope of 3D QSAR methods (CoMFA, CoMSIA) to screen databases are examined. A protocol requiring minimal user intervention has been established to align training and test set molecules using FlexS. As model system isozymes of human carbonic anhydrase (hCA) are used, all results are exemplified stu...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci7002945
更新日期：2008-02-01 00:00:00
abstract：:Chemical structure extraction from documents remains a hard problem because of both false positive identification of structures during segmentation and errors in the predicted structures. Current approaches rely on handcrafted rules and subroutines that perform reasonably well generally but still routinely encounter s...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.8b00669
更新日期：2019-03-25 00:00:00
abstract：:Random Forest regression (RF), Partial-Least-Squares (PLS) regression, Support Vector Machines (SVM), and Artificial Neural Networks (ANN) were used to develop QSPR models for the prediction of aqueous solubility, based on experimental data for 988 organic molecules. The Random Forest regression model predicted aqueou...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci060164k
更新日期：2007-01-01 00:00:00
abstract：:In this work, we present a systematical investigation of the influence of ligand protonation states, stereoisomers, and tautomers on results obtained with the two protein-ligand docking programs GOLD and PLANTS. These different states were generated with a fully automated tool, called SPORES (Structure PrOtonation and...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci800420z
更新日期：2009-06-01 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：:G protein-coupled receptors (GPCRs) represent the largest family of cell-surface receptors and about one-third of the actual targets of clinically used drugs. Following the progress made in the field of GPCRs structural determination, docking-based screening for novel potent and selective ligands is becoming an increa...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci400532b
更新日期：2014-01-27 00:00:00
abstract：:3-Phosphoinositide-dependent protein kinase-1 (PDK1) is a promising target for developing novel anticancer drugs. In order to understand the structure-activity correlation of indolinone-based PDK1 inhibitors, we have carried out a combined molecular docking and three-dimensional quantitative structure-activity relatio...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci800147v
更新日期：2008-09-01 00:00:00
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
doi：10.1021/ci6005307
更新日期：2007-03-01 00:00:00
abstract：:A fully folded functional protein is stabilized by several noncovalent interactions. When a protein undergoes conformational motions, the existing noncovalent interactions may be maintained. They may also break or new interactions may be formed. Knowledge of the dynamical nature of the different types of noncovalent i...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci200302q
更新日期：2011-12-27 00:00:00
abstract：:The modeling of nonlinear descriptor-target relationships is a topic of considerable interest in drug discovery. We, herein, continue reporting the use of the self-organizing map-a nonlinear, topology-preserving pattern recognition technique that exhibits considerable promise in modeling and decoding these relationshi...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci0500841
更新日期：2006-01-01 00:00:00
abstract：:Calcium is involved in important intracellular processes, such as intracellular signaling from cell membrane receptors to the nucleus. Typically, calcium levels are kept at less than 100 nM in the nucleus and cytosol, but some calcium is stored in the endoplasmic reticulum (ER) lumen for rapid release to activate intr...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.6b00475
更新日期：2017-02-27 00:00:00
abstract：:Encapsulation of peptide and protein-based drugs in polymeric nanoparticles is one of the fundamental fields in controlled-release drug delivery systems. The molecular mechanisms of absorption of peptides to the polymeric nanoparticles are still unknown, and there is no precise molecular data on the encapsulation proc...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.8b00641
更新日期：2019-01-28 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：: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：:How well do different classification methods perform in selecting the ligands of a protein target out of large compound collections not used to train the model? Support vector machines, random forest, artificial neural networks, k-nearest-neighbor classification with genetic-algorithm-optimized feature selection, tren...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci050519k
更新日期：2006-05-01 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
abstract：:The cannabinoid receptor subtype 2 (CB2) is a promising therapeutic target for blood cancer, pain relief, osteoporosis, and immune system disease. The recent withdrawal of Rimonabant, which targets another closely related cannabinoid receptor (CB1), accentuates the importance of selectivity for the development of CB2 ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci3003914
更新日期：2013-01-28 00:00:00
abstract：:Reaction databases provide a great deal of useful information to assist planning of experiments but do not provide any interpretation or chemical concepts to accompany this information. In this work, reactions are labeled with experimental conditions, and network analysis shows that consistencies within clusters of da...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00313
更新日期：2019-09-23 00:00:00
abstract：:Distribution patterns of 8411 compounds from 240 Chinese herbs were analyzed in relation to the herbal categories of traditional Chinese medicine (TCM), using Random Forest (RF) and self-organizing maps (SOM). RF was used first to construct TCM profiles of individual compounds, which describe their affinities for 28 m...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci700155t
更新日期：2007-11-01 00:00:00
abstract：:In this study, in order to elucidate the action mechanism of traditional Chinese medicines (TCMs) that exhibit clinical efficacy for type II diabetes mellitus (T2DM), an integrated protocol that combines molecular docking and pharmacophore mapping was employed to find the potential inhibitors from TCM for the T2DM-rel...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci400146u
更新日期：2013-07-22 00:00:00
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
doi：10.1021/acs.jcim.8b00959
更新日期：2019-05-28 00:00:00
abstract：:The effects of paclitaxel (PTX) loading fraction and spatial PTX arrangement on poly(γ-glutamyl-glutamate) paclitaxel (PGG-PTX) aggregation were explored using coarse-grained molecular dynamics. Results show that the PTX loading fraction does not significantly impact aggregation, and the spatial PTX arrangement only a...
journal_title：Journal of chemical information and modeling
pub_type： 信件
doi：10.1021/ci200214m
更新日期：2011-12-27 00:00:00
abstract：:The sensitivity of docking calculations to the geometry of the input ligand was studied. It was found that even small changes in the ligand input conformation can lead to large differences in the geometries and scores of the resulting docked poses. The accuracy of docked poses produced from different ligand input stru...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci9000629
更新日期：2009-07-01 00:00:00
