3,878 results match your criteria Journal of Chemical Information and Modeling [Journal]


Predicting Positions of Bridging Water Molecules in Nucleic Acid-Ligand Complexes.

J Chem Inf Model 2019 Apr 18. Epub 2019 Apr 18.

Over the past two decades, interests in DNA and RNA as drug targets have been growing rapidly. Following the trends observed with protein drug targets, computational approaches for drug design have been developed for this new class of molecules. Our efforts towards the development of a universal docking program, FITTED, led us to focus on nucleic acids. Read More

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http://pubs.acs.org/doi/10.1021/acs.jcim.9b00163
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http://dx.doi.org/10.1021/acs.jcim.9b00163DOI Listing
April 2019
1 Read

Building Quantitative Structure-Activity Relationship Models Using Bayesian Additive Regression Trees.

J Chem Inf Model 2019 Apr 18. Epub 2019 Apr 18.

Quantitative structure-activity relationship (QSAR) is a very commonly used technique for predicting biological activity of a molecule using information contained in the molecular descriptors. The large number of compounds and descriptors and sparseness of descriptors pose important challenges to traditional statistical methods and machine learning (ML) algorithms (such as random forest (RF)) used in this field. Recently, Bayesian Additive Regression Trees (BART), a flexible Bayesian non-parametric regression approach, has been demonstrated to be competitive with widely used ML approaches. Read More

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http://pubs.acs.org/doi/10.1021/acs.jcim.9b00094
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http://dx.doi.org/10.1021/acs.jcim.9b00094DOI Listing
April 2019
1 Read

Dimerization Behavior of Methyl Chlorophyllide a as the Model of Chlorophyll a in Presence of Water Molecules - Theoretical Study.

J Chem Inf Model 2019 Apr 18. Epub 2019 Apr 18.

A dimerization of methyl chlorophyllide a molecules and a role of water in stabilization and properties of methyl chlorophyllide a dimers was studied by means of symmetry-adapted perturbation theory (SAPT), functional-group SAPT (F-SAPT), density-functional theory (DFT), and time-dependent DFT approaches. The quantification of various types of interactions, such as pi-pi stacking, coordinative, and hydrogen bonding by applying the F-SAPT-style energy decomposition scheme shows the major role of the magnesium atom and the chlorin macrocycle in the stability of the complex. The examination of interaction energy components with respect to a mutual orientation of monomers and in the presence or absence of water molecules reveals that the dispersion energy is the main binding factor of the interaction, while water molecules tend to weaken the attraction between methyl chlorophyllide a species. Read More

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http://dx.doi.org/10.1021/acs.jcim.8b00984DOI Listing

Materials Informatics.

J Chem Inf Model 2018 Dec;58(12):2377-2379

Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy , University of North Carolina , Chapel Hill , North Carolina 27599 , United States.

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http://dx.doi.org/10.1021/acs.jcim.8b00927DOI Listing
December 2018

Go-Kit: A Tool To Enable Energy Landscape Exploration of Proteins.

J Chem Inf Model 2019 Apr 12. Epub 2019 Apr 12.

Simons Centre for the Study of Living Machines , National Centre for Biological Sciences, Tata Institute of Fundamental Research , Bellary Road , Bangalore 560065 , India.

Coarse-grained Go̅-like models, based on the principle of minimal frustration, provide valuable insight into fundamental questions in the field of protein folding and dynamics. In conjunction with commonly used molecular dynamics (MD) simulations, energy landscape exploration methods like discrete path sampling (DPS) with Go̅-like models can provide quantitative details of the thermodynamics and kinetics of proteins. Here we present Go-kit, a software that facilitates the setup of MD and DPS simulations of several flavors of Go̅-like models. Read More

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http://dx.doi.org/10.1021/acs.jcim.9b00007DOI Listing

Fantastic Liquids and Where To Find Them: Optimizations of Discrete Chemical Space.

J Chem Inf Model 2019 Apr 19. Epub 2019 Apr 19.

Department of Chemical Engineering , University of Washington , Seattle , Washington 98105 , Unitd States.

We present a computational adaptive learning and design strategy for ionic liquids. In this approach we show that (1) multiple cycles of chemical search via genetic algorithm (GA), property calculation with molecular dynamics, and property modeling with physiochemical descriptors and neural networks (QSPR/NN) lead to overall lower property prediction error rates compared to the original QSPR/NN models; (2) chemical similarity and kernel density estimation are a proxy for QSPR/NN error; and (3) single QSPR/NN models projected onto two-dimensional property space recreate the experimentally observed Pareto optimum frontier and, combined with the GA, lead to new structures with properties beyond the frontier. Read More

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http://dx.doi.org/10.1021/acs.jcim.9b00087DOI Listing

Haptic-assisted interactive molecular docking incorporating receptor flexibility.

J Chem Inf Model 2019 Apr 10. Epub 2019 Apr 10.

Haptic-assisted interactive docking tools immerse the user in an environment where intuition and knowledge can be used to help guide the docking process. Here we present such a tool where the user "holds" a rigid ligand via a haptic device through which they feel interaction forces with a flexible receptor biomolecule. To ensure forces transmitted through the haptic device are smooth and stable, they must be updated at a rate greater than 500 Hz. Read More

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http://dx.doi.org/10.1021/acs.jcim.9b00112DOI Listing

MedusaDock 2.0: Efficient and Accurate Protein-Ligand Docking With Constraints.

J Chem Inf Model 2019 Apr 17. Epub 2019 Apr 17.

Department of Pharmacology , Penn State University College of Medicine , Hershey , Pennsylvania 17033 , United States.

Molecular docking is the key ingredient of virtual drug screening, a promising and cost-effective approach for finding new drugs. A critical limitation of this approach is the inadequate sampling efficiency of both ligand and/or receptor conformations for finding the lowest energy bound state. To circumvent this limitation, we develop a protein-ligand docking methodology capable of incorporating structural constraints, experimentally derived or theoretically predicted, to improve accuracy and efficiency. Read More

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http://dx.doi.org/10.1021/acs.jcim.8b00905DOI Listing

DNAPred: Accurate Identification of DNA-Binding Sites from Protein Sequence by Ensembled Hyperplane-Distance-Based Support Vector Machines.

J Chem Inf Model 2019 Apr 16. Epub 2019 Apr 16.

School of Computer Science and Engineering , Nanjing University of Science and Technology , Xiaolingwei 200 , Nanjing 210094 , P. R. China.

Accurate identification of protein-DNA binding sites is significant for both understanding protein function and drug design. Machine-learning-based methods have been extensively used for the prediction of protein-DNA binding sites. However, the data imbalance problem, in which the number of nonbinding residues (negative-class samples) is far larger than that of binding residues (positive-class samples), seriously restricts the performance improvements of machine-learning-based predictors. Read More

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http://dx.doi.org/10.1021/acs.jcim.8b00749DOI Listing
April 2019
3.738 Impact Factor

Biased Complement Diversity Selection for Effective Exploration of Chemical Space in Hit-Finding Campaigns.

J Chem Inf Model 2019 Apr 3. Epub 2019 Apr 3.

Novartis Institutes for BioMedical Research , 5300 Chiron Way , Emeryville , California 94608 , United States.

The success of hit-finding campaigns relies on many factors, including the quality and diversity of the set of compounds that is selected for screening. This paper presents a generalized workflow that guides compound selections from large compound archives with opportunities to bias the selections with available knowledge in order to improve hit quality while still effectively sampling the accessible chemical space. An optional flag in the workflow supports an explicit complement design function where diversity selections complement a given core set of compounds. Read More

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http://dx.doi.org/10.1021/acs.jcim.9b00048DOI Listing
April 2019
2 Reads

Computational Tools Unravel Putative Sterol Binding Sites in the Lysosomal NPC1 Protein.

J Chem Inf Model 2019 Apr 15. Epub 2019 Apr 15.

Department of Chemistry , Technische Universität Berlin , 10623 Berlin , Germany.

Two proteins have been linked as the critical components in the molecular mechanisms involved in the Niemann Pick type C (NPC) disease: NPC1, a 140 kDa polytopic membrane-bound protein, and the smaller (132 residues), water-soluble NPC2 protein. NPC1 is believed to act in tandem with NPC2, transferring cholesterol and other sterols out of the LE/Lys compartments. Mutations in either NPC1 or NPC2 can lead to an accumulation of cholesterol and lipids in the LE/Lys, the primary phenotype of the NPC disease, but approximately 95% of identified disease-causing mutations have been mapped to the membrane-bound NPC1 protein. Read More

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http://dx.doi.org/10.1021/acs.jcim.9b00186DOI Listing
April 2019
3 Reads

Novel β-keto-enol Pyrazolic Compounds as Potent Antifungal Agents. Design, Synthesis, Crystal Structure, DFT, Homology Modeling, and Docking Studies.

J Chem Inf Model 2019 Apr 10. Epub 2019 Apr 10.

ICGM, UMR 5253, CNRS , Université de Montpellier , ENSCM , Montpellier , 34095 France.

A new family of promising inhibitors bearing β-keto-enol functionality with greatly improved pharmacophore properties has been prepared. Herein, a series of novel derivatives of β-keto-enol group embedded with pyrazolic moiety has been designed and synthesized via a one-step procedure using mixed Claisen condensation in the attempt to develop potential antifungal agents. The structures of the synthesized compounds were confirmed by elemental analysis, FT-IR, ESI/LC-MS, and H and C NMR. Read More

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http://dx.doi.org/10.1021/acs.jcim.8b00828DOI Listing
April 2019
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Transition Metal Ion Interactions with Disordered Amyloid-β Peptides in the Pathogenesis of Alzheimer's Disease: Insights from Computational Chemistry Studies.

J Chem Inf Model 2019 Apr 15. Epub 2019 Apr 15.

Molecular Biotechnology , Turkish-German University , Sahinkaya Caddesi, No. 86, Beykoz , Istanbul 34820 , Turkey.

Monomers and oligomers of the amyloid-β peptide aggregate to form the fibrils found in the brains of Alzheimer's disease patients. These monomers and oligomers are largely disordered and can interact with transition metal ions, affecting the mechanism and kinetics of amyloid-β aggregation. Due to the disordered nature of amyloid-β, its rapid aggregation, as well as solvent and paramagnetic effects, experimental studies face challenges in the characterization of transition metal ions bound to amyloid-β monomers and oligomers. Read More

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http://dx.doi.org/10.1021/acs.jcim.8b00983DOI Listing
April 2019
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A Coarse-Grained Molecular Dynamics Approach to the Study of the Intrinsically Disordered Protein α-Synuclein.

J Chem Inf Model 2019 Apr 12. Epub 2019 Apr 12.

Institut Universitari d'Investigació en Ciències de la Salut (IUNICS), Departament de Química , Universitat de les Illes Balears , 07122 Palma de Mallorca , Spain.

Intrinsically disordered proteins (IDPs) are not well described by a single 3D conformation but by an ensemble of them, which makes their structural characterization especially challenging, both experimentally and computationally. Most all-atom force fields are designed for folded proteins and give too compact IDP conformations. α-Synuclein is a well-known IDP because of its relation to Parkinson's disease (PD). Read More

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http://pubs.acs.org/doi/10.1021/acs.jcim.8b00921
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http://dx.doi.org/10.1021/acs.jcim.8b00921DOI Listing
April 2019
3 Reads

PythoMS: A Python Framework To Simplify and Assist in the Processing and Interpretation of Mass Spectrometric Data.

J Chem Inf Model 2019 Apr 11. Epub 2019 Apr 11.

Department of Chemistry , University of Victoria , P.O. Box 3065, Victoria , BC V8W 3V6 , Canada.

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 framework introduces a library of classes and a variety of scripts that quickly perform time-consuming tasks: making proprietary output readable; binning intensity vs time data to simulate longer scan times (and hence reduce noise); calculating theoretical isotope patterns and overlaying them in histogram form on experimental data (an approach that works even for overlapping signals); rendering videos that enable zooming into the baseline of intensity vs time plots (useful to make sense of data collected over a large dynamic range) or that depict the evolution of different species in a time-lapse format; calculating aggregates; and providing a quick first-pass at identifying fragments in MS/MS spectra. Read More

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http://pubs.acs.org/doi/10.1021/acs.jcim.9b00055
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http://dx.doi.org/10.1021/acs.jcim.9b00055DOI Listing
April 2019
6 Reads

Understanding the Mechanism of Direct Activation of AMP-Kinase: Toward a Fine Allosteric Tuning of the Kinase Activity.

J Chem Inf Model 2019 Apr 12. Epub 2019 Apr 12.

Department of Nutrition, Food Science and Gastronomy, Faculty of Pharmacy and Food Sciences, Institute of Biomedicina (IBUB) and Institute of Theoretical and Computational Chemistry (IQTCUB) , University of Barcelona , Santa Coloma de Gramenet 08921 , Spain.

Mammalian AMP-activated protein kinase (AMPK) is a Ser/Thr protein kinase with a key role as a sensor in cellular energy homeostasis. It has a major role in numerous metabolic disorders, such as type 2 diabetes, obesity, and cancer, and hence it has gained progressive interest as a potential therapeutic target. AMPK is a heterotrimeric enzyme composed by an α-catalytic subunit and two regulatory subunits, β and γ. Read More

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http://dx.doi.org/10.1021/acs.jcim.8b00890DOI Listing

Developing a Transferable Coarse-Grained Model for the Prediction of Thermodynamic, Structural, and Mechanical Properties of Polyimides at Different Thermodynamic State Points.

J Chem Inf Model 2019 Apr 11. Epub 2019 Apr 11.

Beijing National Laboratory for Molecular Sciences, Joint Laboratory of Polymer Sciences and Materials, State Key Laboratory of Polymer Physics and Chemistry , Institute of Chemistry, Chinese Academy of Sciences , Beijing 100190 , China.

In the present work, we develop a coarse-grained (CG) model for polyimide (PI) at 800 K and 1 atm by applying iterative Boltzmann inversion (IBI) and the density correction method to derive the bonded and nonbonded interaction potentials. Although the CG force field is built at a single thermodynamic state point without any temperature correction, the CG model possesses a rather favorable temperature transferability in a wide temperature range of 300-800 K at P = 1 atm and a good pressure transferability to some extent in a certain pressure range from 0.1 to 30 MPa. Read More

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http://dx.doi.org/10.1021/acs.jcim.8b00887DOI Listing

Theoretical Investigation of Steric Effect Influence on Reactivity of Substituted Butadienes with Bromocyclobutenone.

J Chem Inf Model 2019 Apr 9. Epub 2019 Apr 9.

Department of Chemistry , Bharathidasan Institute of Technology (A Constituent College of Anna University-Chennai) , Tiruchirappalli - 620 024 , Tamil Nadu , India.

The Diels-Alder reaction (DA) between various mono- and disubstituted 1,3-butadiene (Dn-1 to Dn-10) and 2-bromocyclobutenone (DPh) was carried out in gas phase using density functional theory (DFT) at the M06-2X/6-31+g** level. The reaction was found to proceed through a concerted asynchronous transition state. Further, the asynchronous and early nature of the transition state was clearly pinpointed with the frontier molecular orbital (FMO) and bond order index (BOI) analyses. Read More

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http://dx.doi.org/10.1021/acs.jcim.9b00177DOI Listing

Ligand-Based Virtual Screening Using Graph Edit Distance as Molecular Similarity Measure.

J Chem Inf Model 2019 Apr 10. Epub 2019 Apr 10.

Departament d'Enginyeria Informàtica i Matemàtiques , Universitat Rovira i Virgili , Tarragona , Catalunya 43007 , Spain.

Extended reduced graphs provide summary representations of chemical structures using pharmacophore-type node descriptions to encode the relevant molecular properties. Commonly used similarity measures using reduced graphs convert these graphs into 2D vectors like fingerprints, before chemical comparisons are made. This study investigates the effectiveness of a graph-only driven molecular comparison by using extended reduced graphs along with graph edit distance methods for molecular similarity calculation as a tool for ligand-based virtual screening applications, which estimate the bioactivity of a chemical on the basis of the bioactivity of similar compounds. Read More

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http://dx.doi.org/10.1021/acs.jcim.8b00820DOI Listing
April 2019
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Determination of Absolute Stereochemistry of Flexible Molecules Using a Vibrational Circular Dichroism Spectra Alignment Algorithm.

J Chem Inf Model 2019 Mar 27. Epub 2019 Mar 27.

Laboratory of Physical Chemistry , ETH Zürich , Vladimir-Prelog-Weg 2 , 8093 Zürich , Switzerland.

Experimental determination of the absolute stereochemistry of chiral molecules has been a fundamental challenge in natural sciences for decades. Vibrational circular dichroism (VCD) spectroscopy represents an attractive alternative to traditional methods like X-ray crystallography due to the use of molecules in solution. The interpretation of measured VCD spectra and thus the assignment of the absolute configuration relies on quantum-mechanical calculations. Read More

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http://dx.doi.org/10.1021/acs.jcim.8b00789DOI Listing

From Quantum Chemistry to Networks in Biology: A Graph Spectral Approach to Protein Structure Analyses.

J Chem Inf Model 2019 Apr 9. Epub 2019 Apr 9.

Molecular Biophysics Unit , Indian Institute of Science , C V Raman Road , Bengaluru , Karnataka 560012 , India.

In this perspective article, we present a multidisciplinary approach for characterizing protein structure networks. We first place our approach in its historical context and describe the manner in which it synthesizes concepts from quantum chemistry, biology of polymer conformations, matrix mathematics, and percolation theory. We then explicitly provide the method for constructing the protein structure network in terms of noncovalently interacting amino acid side chains and show how a mine of information can be obtained from the graph spectra of these networks. Read More

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http://pubs.acs.org/doi/10.1021/acs.jcim.9b00002
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http://dx.doi.org/10.1021/acs.jcim.9b00002DOI Listing
April 2019
2 Reads

Efficient Corrections for DFT Noncovalent Interactions Based on Ensemble Learning Models.

J Chem Inf Model 2019 Apr 8. Epub 2019 Apr 8.

Department of Chemistry , The University of Hong Kong , Hong Kong , China.

Machine learning has exhibited powerful capabilities in many areas. However, machine learning models are mostly database dependent, requiring a new model if the database changes. Therefore, a universal model is highly desired to accommodate the widest variety of databases. Read More

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http://dx.doi.org/10.1021/acs.jcim.8b00878DOI Listing
April 2019
1 Read

Doping Effects on the Performance of Paired Metal Catalysts for the Hydrogen Evolution Reaction.

J Chem Inf Model 2019 Apr 9. Epub 2019 Apr 9.

Centre for Theoretical and Computational Molecular Science, The Australian Institute for Bioengineering and Nanotechnology , The University of Queensland , Brisbane , Queensland 4072 , Australia.

Metal heteroatoms dispersed in nitrogen-doped graphene display promising catalytic activity for fuel cell reactions such as the hydrogen evolution reaction (HER). Here we explore the effects of the dopant concentration on the synergistic catalytic behavior of a paired metal atom active site comprising Co and Pt atoms that have been shown to be particularly active catalysts in these materials. The metals are coordinated to six atoms in a vacancy of N-doped graphene. Read More

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http://dx.doi.org/10.1021/acs.jcim.9b00179DOI Listing

Protein-Ligand Complexes as Constrained Dynamical Systems.

J Chem Inf Model 2019 Apr 4. Epub 2019 Apr 4.

Department of Computational and Systems Biology, School of Medicine , University of Pittsburgh , Pittsburgh , Pennsylvania 15261 , United States.

This study focuses on how the low-frequency end of the vibrational spectrum related to the functional motions changes as a protein binds to a small ligand(s). Our recently proposed residue-specific (RESPEC) elastic network model provides a natural laboratory for this aim due to its systematic mixed coarse-graining approach and parametrization. Current analysis on a large data set of protein-ligand complexes reveals a universal curve enclosing the frequency distributions, which bears the features of previous computational and experimental studies. Read More

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http://dx.doi.org/10.1021/acs.jcim.8b00946DOI Listing

Multitask Modeling with Confidence Using Matrix Factorization and Conformal Prediction.

J Chem Inf Model 2019 Apr 5. Epub 2019 Apr 5.

Alzheimer's Research UK UCL Drug Discovery Institute , University College London , Cruciform Building, Gower Street , London , WC1E 6BT , U.K.

Multitask prediction of bioactivities is often faced with challenges relating to the sparsity of data and imbalance between different labels. We propose class conditional (Mondrian) conformal predictors using underlying Macau models as a novel approach for large scale bioactivity prediction. This approach handles both high degrees of missing data and label imbalances while still producing high quality predictive models. Read More

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http://dx.doi.org/10.1021/acs.jcim.9b00027DOI Listing

Drug Analogs from Fragment-Based Long Short-Term Memory Generative Neural Networks.

J Chem Inf Model 2019 Apr 8. Epub 2019 Apr 8.

Department of Chemistry and Biochemistry , University of Bern , Freiestrasse 3 , 3012 Bern , Switzerland.

Several recent reports have shown that long short-term memory generative neural networks (LSTM) of the type used for grammar learning efficiently learn to write Simplified Molecular Input Line Entry System (SMILES) of druglike compounds when trained with SMILES from a database of bioactive compounds such as ChEMBL and can later produce focused sets upon transfer learning with compounds of specific bioactivity profiles. Here we trained an LSTM using molecules taken either from ChEMBL, DrugBank, commercially available fragments, or from FDB-17 (a database of fragments up to 17 atoms) and performed transfer learning to a single known drug to obtain new analogs of this drug. We found that this approach readily generates hundreds of relevant and diverse new drug analogs and works best with training sets of around 40,000 compounds as simple as commercial fragments. Read More

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http://dx.doi.org/10.1021/acs.jcim.8b00902DOI Listing

Theoretical Design of D-π-A-A Sensitizers with Narrow Band Gap and Broad Spectral Response Based on Boron Dipyrromethene for Dye-Sensitized Solar Cells.

J Chem Inf Model 2019 Apr 3. Epub 2019 Apr 3.

School of Chemistry and Material Science , Shanxi Normal University , Linfen 041000 , P.R. China.

Dye-sensitized solar cells based on boron dipyrromethene (BODIPY) have gained widespread attention in recent years because of their easy structural modification, strong light absorption, and photostability. In this paper, a series of dyes with single or double acceptors based on the BODIPY framework have been designed and compared by density functional theory calculation. Results show that the dyes with double acceptors exhibit smaller band gap and broader red-shift absorption peaks than their counterparts with single acceptors. Read More

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http://dx.doi.org/10.1021/acs.jcim.9b00187DOI Listing
April 2019
1 Read

Modeling Boronic Acid Based Flourescent Saccharide Sensors: Computational Investigation of d-Fructose Binding to Dimethylaminomethylphenylboronic Acid (DMPBA).

J Chem Inf Model 2019 Mar 25. Epub 2019 Mar 25.

Designing organic saccharide sensors for use in aqueous solution is a non-trivial endeavor. Incorporation of hydrogen bonding groups on a sensor's receptor unit to target saccharides is an obvious strategy, but not one that is likely to ensure analyte-receptor interactions over analyte-solvent or receptor-solvent interactions. Phenylboronic acids are known to reversibly and covalently bind saccharides (diols in general) with highly selective affinity in aqueous solution. Read More

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http://dx.doi.org/10.1021/acs.jcim.8b00987DOI Listing

RISC: Rapid Inverted-Index Based Search of Chemical Fingerprints.

J Chem Inf Model 2019 Apr 19. Epub 2019 Apr 19.

Department of Computer Science , IIT-Delhi , New Delhi , 110016 , India.

The ability to search for a query molecule on massive molecular repositories is a fundamental task in chemoinformatics and drug-discovery. Chemical fingerprints are commonly used to characterize the structure and properties of molecules. Some fingerprints, particularly unfolded fingerprints, are often of extreme high dimension and sparse where only few features have a positive value. Read More

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http://dx.doi.org/10.1021/acs.jcim.9b00069DOI Listing

Cosolvent Impurities in SWCNT Nanochannel Confinement: Length Dependence of Water Dynamics Investigated with Atomistic Simulations.

J Chem Inf Model 2019 Apr 3. Epub 2019 Apr 3.

Department of Biological Sciences , Indian Institute of Science Education and Research Kolkata , Mohanpur 741 246 , India.

The advent of nanotechnology has seen a growing interest in the nature of fluid flow and transport under nanoconfinement. The present study leverages fully atomistic molecular dynamics (MD) simulations to study the effect of nanochannel length and intrusion of molecules of the organic solvent, hexafluoro-2-propanol (HFIP), on the dynamical characteristics of water within it. Favorable interactions of HFIP with the nanochannels comprised of single-walled carbon nanotubes traps them over time scales greater than 100 ns, and confinement confers small but distinguishable spatial redistribution between neighboring HFIP pairs. Read More

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http://dx.doi.org/10.1021/acs.jcim.8b00889DOI Listing

Cyclohexane-Based Scaffold Molecules Acting as Anion Transport, Anionophores, via Noncovalent Interactions.

J Chem Inf Model 2019 Apr 3. Epub 2019 Apr 3.

School of Chemistry , Trinity Biomedical Sciences, Trinity College Dublin , 152-160 Pearse Street , Dublin 2 , Ireland.

A theoretical study of a variety of cyclohexane-based anion transporters interacting with the chloride anion has been conducted using density functional theory. The calculations have been performed in the gas phase but also, in order to describe the solvation effects on the interaction, two different solvents-chloroform and dimethylsulfoxide-have been taken into account. Gas-phase interaction energies within the complexes are found to be up to 400 kJ/mol, while, when solvent effects are considered, the interaction energy values decreased drastically concomitantly with an elongation in the interatomic distances. Read More

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http://dx.doi.org/10.1021/acs.jcim.9b00154DOI Listing
April 2019
1 Read

CovaDOTS: In Silico Chemistry-Driven Tool to Design Covalent Inhibitors Using a Linking Strategy.

J Chem Inf Model 2019 Apr 5. Epub 2019 Apr 5.

Aix Marseille Univ, CNRS, Inserm, Institut Paoli Calmettes, CRCM , Marseille CEDEX 09 13273 , France.

We recently reported an integrated fragment-based optimization strategy called DOTS (Diversity Oriented Target-focused Synthesis) that combines automated virtual screening (VS) with semirobotized organic synthesis coupled to in vitro evaluation. The molecular modeling part consists of hit-to-lead chemistry, based on the growing paradigm. Here, we have extended the applicability of the DOTS strategy by adding new functionalities, allowing a generic chemistry-driven linking approach with a particular emphasis on covalent drugs. Read More

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http://dx.doi.org/10.1021/acs.jcim.8b00960DOI Listing

Machine Learning in Drug Discovery.

J Chem Inf Model 2019 Mar;59(3):945-946

Universität Hamburg , ZBH-Center for Bioinformatics , 20146 Hamburg , Germany.

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http://dx.doi.org/10.1021/acs.jcim.9b00136DOI Listing

Machine Learning Prediction of H Adsorption Energies on Ag Alloys.

J Chem Inf Model 2019 Apr 2. Epub 2019 Apr 2.

Adsorption energies on surfaces are excellent descriptors of their chemical properties, including their catalytic performance. High-throughput adsorption energy predictions can therefore help accelerate first-principles catalyst design. To this end, we present over 5000 DFT calculations of H adsorption energies on dilute Ag alloys and describe a general machine learning approach to rapidly predict H adsorption energies for new Ag alloy structures. Read More

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http://dx.doi.org/10.1021/acs.jcim.8b00657DOI Listing
April 2019
6 Reads

A Molecular Dynamics Investigation of the Thermostability of Cold-Sensitive I707L KlenTaq1 DNA Polymerase and Its Wild-Type Counterpart.

J Chem Inf Model 2019 Apr 8. Epub 2019 Apr 8.

Department of Chemistry, Gottwald Center for the Sciences , University of Richmond , Richmond , Virginia 23713 , United States.

DNA polymerase I from Thermus aquaticus ( Taq DNA polymerase) is useful for polymerase chain reactions because of its exceptional thermostability; however, its activity at low temperatures can cause amplification of unintended products. Mutation of isoleucine 707 to leucine (I707L) slows Taq DNA polymerase at low temperatures, which decreases unwanted amplification due to mispriming. In this work, unrestrained molecular dynamics (MD) simulations were performed on I707L and wild-type (WT) Taq DNA polymerase at 341 and 298 K to determine how the mutation affects the dynamic nature of the protein. Read More

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http://dx.doi.org/10.1021/acs.jcim.9b00022DOI Listing

Magnesium-Based Oxyfluoride Superatoms: Design, Structure, and Electronic Properties.

Authors:
Celina Sikorska

J Chem Inf Model 2019 Apr 15. Epub 2019 Apr 15.

Laboratory of Molecular Modeling, Department of Theoretical Chemistry, Faculty of Chemistry , University of Gdansk , Wita Stwosza 63 , 80-308 Gdansk , Poland.

The ability of mixed ligands to form stable dinuclear and trinuclear magnesium-based superatoms has been investigated theoretically. The MgFO and MgFO systems (where m = 1-3) were found able to form stable and strongly bound anionic clusters, and those assumptions were validated by (i) the analysis of the geometrical stability; (ii) the estimated Gibbs free energies for the most probable disproportion paths these clusters might be vulnerable to (which allows examining their thermodynamic stabilities); (iii) the localization of the electron density; and (iv) the adiabatic electron affinity (AEA), vertical electron detachment energy (VDE), and adiabatic electron detachment energy (ADE) values calculated for the studied systems. It is demonstrated that the stability of the anionic daughters of these clusters increases with the number of electronegative ligands, and Mg FO ( n = 2, 3; m = 1-3) clusters are stable against electron emission. Read More

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http://dx.doi.org/10.1021/acs.jcim.9b00083DOI Listing

Deep Learning and Random Forest Approach for Finding the Optimal Traditional Chinese Medicine Formula for Treatment of Alzheimer's Disease.

J Chem Inf Model 2019 Apr 2. Epub 2019 Apr 2.

School of Intelligent Systems Engineering , Sun Yat-sen University , Shenzhen 510275 , China.

It has demonstrated that glycogen synthase kinase 3β (GSK3β) is related to Alzheimer's disease (AD). On the basis of the world largest traditional Chinese medicine (TCM) database, a network-pharmacology-based approach was utilized to investigate TCM candidates that can dock well with multiple targets. Support vector machine (SVM) and multiple linear regression (MLR) methods were utilized to obtain predicted models. Read More

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http://dx.doi.org/10.1021/acs.jcim.9b00041DOI Listing

GuacaMol: Benchmarking Models for de Novo Molecular Design.

J Chem Inf Model 2019 Mar 19;59(3):1096-1108. Epub 2019 Mar 19.

BenevolentAI , 4-8 Maple Street , W1T 5HD London , U.K.

De novo design seeks to generate molecules with required property profiles by virtual design-make-test cycles. With the emergence of deep learning and neural generative models in many application areas, models for molecular design based on neural networks appeared recently and show promising results. However, the new models have not been profiled on consistent tasks, and comparative studies to well-established algorithms have only seldom been performed. Read More

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http://dx.doi.org/10.1021/acs.jcim.8b00839DOI Listing

MD Simulation Investigation on the Binding Process of Smoke-Derived Germination Stimulants to Its Receptor.

J Chem Inf Model 2019 Mar 26. Epub 2019 Mar 26.

International Joint Research Laboratory of Nano-Micro Architecture Chemistry, Institute of Theoretical Chemistry , Jilin University , Changchun 130023 , Jilin , People's Republic of China.

Karrikins (KARs) are a class of smoke-derived seed germination stimulants with great significance in both agriculture and plant biology. By means of direct binding to the receptor protein KAI2, the compounds can initiate the KAR signal transduction pathway, hence triggering germination of the dormant seeds in the soil. In the research, several molecular dynamics (MD) simulation techniques were properly integrated to investigate the binding process of KAR to KAI2 and reveal the details of the whole binding event. Read More

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http://dx.doi.org/10.1021/acs.jcim.8b00844DOI Listing
March 2019
3 Reads

Holo-like and Druggable Protein Conformations from Enhanced Sampling of Binding Pocket Volume and Shape.

J Chem Inf Model 2019 Mar 28. Epub 2019 Mar 28.

Dipartimento di Fisica , Università di Cagliari, Cittadella Universitaria , I- 09042 Monserrato (CA) , Italy.

Understanding molecular recognition of small molecules by proteins in atomistic detail is key for drug design. Molecular docking is a widely used computational method to mimic ligand-protein association in silico. However, predicting conformational changes occurring in proteins upon ligand binding is still a major challenge. Read More

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http://dx.doi.org/10.1021/acs.jcim.8b00730DOI Listing

Discovery of Novel Potential Human Targets of Resveratrol by Inverse Molecular Docking.

J Chem Inf Model 2019 Mar 29. Epub 2019 Mar 29.

National Institute of Chemistry , Hajdrihova 19 , SI-1000 Ljubljana , Slovenia.

Resveratrol is a polyphenol known for its antioxidant and anti-inflammatory properties, which support its use as a treatment for variety of diseases. There are already known connections of resveratrol to chemoprevention of cancer because of its ability to prevent tumor initiation and inhibit tumor promotion and progression. Resveratrol is also believed to be important in cardiovascular diseases and neurological disorders, such as Alzheimer's disease. Read More

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http://dx.doi.org/10.1021/acs.jcim.8b00981DOI Listing

Iterative Solvers for Empirical Partial Atomic Charges: Breaking the Curse of Cubic Numerical Complexity.

J Chem Inf Model 2019 Apr 3. Epub 2019 Apr 3.

Department of Chemistry , Lomonosov Moscow State University , Moscow 119991 , Russian Federation.

Rational drug design involves a vast amount of computations to get thermodynamically reliable results and often relies on atomic charges as a means to model electrostatic interactions within the system. Computational inefficiency often hampers the development of new and wider dissemination of the known methods; thus, any source to speed up the calculations without a sacrifice in quality is warranted. At the heart of many empirical methods of calculating atomic charges is the solution of a system of linear algebraic equations (SLAE). Read More

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http://dx.doi.org/10.1021/acs.jcim.8b00848DOI Listing

The Role of Substituents in Optical Rotation of Oxiranes, Oxetanes, and Oxathietanes.

J Chem Inf Model 2019 Mar 27. Epub 2019 Mar 27.

Department of Physical Chemistry , University of Santiago de Compostela , E-15782 Santiago de Compostela , Spain.

Taking as examples a series of oxiranes, oxetanes, and oxathietanes with different substituents, we study in a systematic way the role that the latter play on the optical rotation of the molecules. For this, we use time-dependent density functional theory together with a hierarchy of Dunning's basis sets. The B3LYP and CAM-B3LYP exchange-correlation functionals are employed. Read More

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http://dx.doi.org/10.1021/acs.jcim.8b00970DOI Listing

Computational Models for Activated Human MEK1: Identification of Key Active Site Residues and Interactions.

J Chem Inf Model 2019 Mar 27. Epub 2019 Mar 27.

Department of Chemistry and Biochemistry , California Polytechnic State University , San Luis Obispo , California 93407 , United States.

MEK1 is a protein kinase in the MAPK cellular signaling pathway that is notable for its dual specificity and its potential as a drug target for a variety of cancer therapies. While much is known about the key role of MEK1 in signaling events, understanding of the structural features that sustain MEK1 function remains limited because of the absence of crystal or NMR structural insights into the phosphorylated and activated form of MEK1. In this work, homology modeling was used to overcome this limitation and generate computational models of the doubly phosphorylated active MEK1 conformation. Read More

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http://dx.doi.org/10.1021/acs.jcim.8b00989DOI Listing
March 2019
1 Read

Computational Methods Used to Explore Transport Events in Biological Systems.

J Chem Inf Model 2019 Mar 28. Epub 2019 Mar 28.

Centre of New Technologies , University of Warsaw , S. Banacha 2c , 02-097 Warsaw , Poland.

Transport of various molecules facilitated with membrane proteins is necessary for maintaining homeostasis in living cells. In humans, dysfunction of these proteins leads to many diseases. Thus, understanding how the membrane proteins function may help using them as therapeutic targets. Read More

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http://dx.doi.org/10.1021/acs.jcim.8b00974DOI Listing
March 2019
1 Read

Planarity or Nonplanarity: Modulating Guanidine Derivatives as α-Adrenoceptors Ligands.

J Chem Inf Model 2019 Mar 27. Epub 2019 Mar 27.

School of Chemistry , Trinity College Dublin , 152-160 Pearse Street , Dublin 2 , Ireland.

A theoretical study has been carried out at the M062X/6-311++G(d,p) computational level to search for a rationale on ligands' affinity toward α-adrenoceptors by estimating the nature and strength of intramolecular hydrogen bonds potentially formed (by means of the QTAIM and NBO approaches) as well as the degree of deviation from planarity that could be observed in some of the compounds. Four different families have been studied: thiophen-2-yl, 3-carboxylatethiophen-2-yl esters, 3-cyanothiophen-2-yl, and 2-thiazolyl guanidinium derivatives. In the case of the thiophen-2-yl guanidines not substituted in the 3 position, nonplanarity was always observed, whereas in the thiazole series, intramolecular hydrogen bonds were identified between the guanidinium and the thiazole ring forcing the systems to planarity. Read More

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http://dx.doi.org/10.1021/acs.jcim.9b00140DOI Listing

DeepIce: A Deep Neural Network Approach To Identify Ice and Water Molecules.

J Chem Inf Model 2019 Mar 27. Epub 2019 Mar 27.

Department of Physics , King's College London , Strand , London WC2R 2LS , United Kingdom.

Computer simulation studies of multiphase systems rely on the accurate identification of local molecular structures and arrangements in order to extract useful insights. Local order parameters, such as Steinhardt parameters, are widely used for this identification task; however, the parameters are often tailored to specific local structural geometries and generalize poorly to new structures and distorted or undercoordinated bonding environments. Motivated by the desire to simplify the process and improve the accuracy, we introduce DeepIce, a novel deep neural network designed to identify ice and water molecules, which can be generalized to new structures where multiple bonding environments are present. Read More

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http://dx.doi.org/10.1021/acs.jcim.9b00005DOI Listing

Molecular Dynamics Simulations of PAMAM and PPI Dendrimers Using the GROMOS-Compatible 2016H66 Force Field.

J Chem Inf Model 2019 Mar 26. Epub 2019 Mar 26.

Instituto de Química , Universidade Federal do Rio de Janeiro , Rio de Janeiro , 21941-909 , Brazil.

A systematic evaluation of the accuracy of the GROMOS-compatible 2016H66 force field in the simulation of dendrimers is performed. More specifically, the poly(amido amine) (PAMAM) and the poly(propyleneimine) (PPI) are considered because of the availability of experimental data and simulation results in the literature. A total of 36 molecular systems are simulated and the radius of gyration, asphericity, density profiles, and the self-diffusion coefficient are monitored in terms of the generation number and pH (low, medium, and high) condition. Read More

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http://dx.doi.org/10.1021/acs.jcim.8b00911DOI Listing