keyword
MENU ▼
Read by QxMD icon Read
search

Computational drug design

keyword
https://www.readbyqxmd.com/read/29156381/structure-based-methods-to-predict-mutational-resistance-to-diarylpyrimidine-non-nucleoside-reverse-transcriptase-inhibitors
#1
Syeda Maryam Azeem, Alecia N Muwonge, Nehaben Thakkar, Kristina W Lam, Kathleen M Frey
Resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) is a leading cause of HIV treatment failure. Often included in antiviral therapy, NNRTIs are chemically diverse compounds that bind an allosteric pocket of enzyme target reverse transcriptase (RT). Several new NNRTIs incorporate flexibility in order to compensate for lost interactions with amino acid conferring mutations in RT. Unfortunately, even successful inhibitors such as diarylpyrimidine (DAPY) inhibitor rilpivirine are affected by mutations in RT that confer resistance...
November 9, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/29155577/identification-of-conserved-water-sites-in-protein-structures-for-drug-design
#2
Marko Jukic, Janez Konc, Stanislav Gobec, Dusanka Janezic
Identification of conserved waters in protein structures is a challenging task with applications in molecular docking and protein stability prediction. As an alternative to computationally demanding simulations of proteins in water, experimental co-crystallized waters in the Protein Data Bank (PDB) in combination with a local structure alignment algorithm can be used for reliable prediction of conserved water sites. We developed the ProBiS H2O approach based on previously developed ProBiS algorithm, which enables identification of conserved water sites in proteins using experimental protein structures from the PDB or a set of custom protein structures available to the user...
November 20, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/29154882/interaction-of-novel-twin-tailed-oxy-diester-functionalized-surfactant-with-lysozyme-spectroscopic-and-computational-perspective
#3
Imtiyaz Ahmad Bhat, Waseem Feeroze Bhat, Mohd Akram, Kabir-Ud-Din
Herein, we have examined the interaction of oxy-diester novel twin tailed (gemini) surfactant, 2,2(')-[(oxybis(ethane-1,2-diyl))bis(oxy)]bis(N-hexadecyl-N,Ndimethyl-2-oxoethanaminium) dichloride (C16-E2O-C16) with hen egg white lysozyme (HEWL), utilizing a spectroscopic and molecular docking techniques. Steady-state fluorescence infers ground state C16-E2O-C16-HEWL complex formation. Other spectroscopic results validated the conformational, structural and micro-environmental changes in HEWL upon interaction with C16-E2O-C16...
November 14, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29150765/finite-element-design-optimization-of-a-hyaluronic-acid-based-hydrogel-drug-delivery-device-for-improved-retention
#4
Jourdan Colter, Barbara Wirostko, Brittany Coats
Drug-loaded hydrogel devices are emerging as an effective means of localized and sustained drug delivery for the treatment of corneal conditions and injuries. One such device uses a novel, thiolated crosslinked carboxymethylated, hyaluronic acid-based hydrogel (CMHA-S) film to deliver drug to the ocular surface upon placement into the inferior fornix of the eye. While proven to be very safe and effective, the CMHA-S film tends to dislodge in the highly-lubricated ocular environment, thereby reducing drug delivery efficiency and drug efficacy...
November 17, 2017: Annals of Biomedical Engineering
https://www.readbyqxmd.com/read/29149726/protein-structure-based-drug-design-from-docking-to-molecular-dynamics
#5
REVIEW
Paweł Śledź, Amedeo Caflisch
Recent years have witnessed rapid developments of computer-aided drug design methods, which have reached accuracy that allows their routine practical applications in drug discovery campaigns. Protein structure-based methods are useful for the prediction of binding modes of small molecules and their relative affinity. The high-throughput docking of up to 10(6) small molecules followed by scoring based on implicit-solvent force field can robustly identify micromolar binders using a rigid protein target. Molecular dynamics with explicit solvent is a low-throughput technique for the characterization of flexible binding sites and accurate evaluation of binding pathways, kinetics, and thermodynamics...
November 14, 2017: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/29147555/what-can-machine-learning-do-for-antimicrobial-peptides-and-what-can-antimicrobial-peptides-do-for-machine-learning
#6
REVIEW
Ernest Y Lee, Michelle W Lee, Benjamin M Fulan, Andrew L Ferguson, Gerard C L Wong
Antimicrobial peptides (AMPs) are a diverse class of well-studied membrane-permeating peptides with important functions in innate host defense. In this short review, we provide a historical overview of AMPs, summarize previous applications of machine learning to AMPs, and discuss the results of our studies in the context of the latest AMP literature. Much work has been recently done in leveraging computational tools to design new AMP candidates with high therapeutic efficacies for drug-resistant infections...
December 6, 2017: Interface Focus
https://www.readbyqxmd.com/read/29145931/in-vitro-and-in-silico-approaches-to-study-cytochrome-p450-mediated-interactions
#7
Boon Hooi Tan, Yan Pan, Amelia Nathania Dong, Chin Eng Ong
In vitro and in silico models of drug metabolism are utilized regularly in the drug research and development as tools for assessing pharmacokinetic variability and drug-drug interaction risk. The use of in vitro and in silico predictive approaches offers advantages including guiding rational design of clinical drug-drug interaction studies, minimization of human risk in the clinical trials, as well as cost and time savings due to lesser attrition during compound development process. This article gives a review of some of the current in vitro and in silico methods used to characterize cytochrome P450(CYP)-mediated drug metabolism for estimating pharmacokinetic variability and the magnitude of drug-drug interactions...
2017: Journal of Pharmacy & Pharmaceutical Sciences: a Publication of the Canadian Society for Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29145692/the-investigation-on-resorcinarenes-towards-either-inhibiting-or-promoting-insulin-fibrillation
#8
Xu Han, Chuan Tian, Ingrid Gandra, Valeria Eslava, Diana Galindres, Edgar Vargas, Roger Leblanc
Different tail enigneered resorcinarenes have been examined towards the insulin fibrillation via experimental and computational studies. The resorcinarene showed a promising effect on the inhibition of insulin fibrillalition via ThT assay, CD spectra, and AFM images. Both ThT assay and computational results indicate the tail from the resorcinarene has an impact on insulin fibrillation by either inhibition or promotion because of the resident position on insulin. These observations have significant biological implications in the design of lead drug molecules as well as the development of potential therapeutic strategies...
November 16, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29143485/synthesis-molecular-modeling-and-biological-evaluation-of-4-5-aryl-3-thiophen-2-yl-4-5-dihydro-1h-pyrazol-1-yl-benzenesulfonamides-towards-acetylcholinesterase-carbonic-anhydrase-i-and-ii-enzymes
#9
Cem Yamali, Halise Inci Gul, Abdulilah Ece, Parham Taslimi, Ilhami Gulcin
In the present study, 4-[5-aryl-3-(thiophen-2-yl)-4,5-dihydro-1H-pyrazol-1-yl] benzenesulfonamides were synthesized and inhibition effects on AChE, hCA I and hCA II were evaluated. Ki values of the compounds towards hCA I were in the range of 24.2±4.6-49.8±12.8 nM while they were in the range of 37.3±9.0-65.3±16.7 nM towards hCA II. Ki values of the Acetazolamide were 282.1±19.7 nM and 103.60±27.6 nM towards both isoenzymes, respectively. The compounds inhibited AChE with Ki in the range of 22.7±10.3-109...
November 16, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/29143270/an-efficient-computer-aided-structural-elucidation-strategy-for-mixtures-using-an-iterative-dynamic-programming-algorithm
#10
Bo-Han Su, Meng-Yu Shen, Yeu-Chern Harn, San-Yuan Wang, Alioune Schurz, Chieh Lin, Olivia A Lin, Yufeng J Tseng
The identification of chemical structures in natural product mixtures is an important task in drug discovery but is still a challenging problem, as structural elucidation is a time-consuming process and is limited by the available mass spectra of known natural products. Computer-aided structure elucidation (CASE) strategies seek to automatically propose a list of possible chemical structures in mixtures by utilizing chromatographic and spectroscopic methods. However, current CASE tools still cannot automatically solve structures for experienced natural product chemists...
November 15, 2017: Journal of Cheminformatics
https://www.readbyqxmd.com/read/29142438/molecular-simulation-based-combinatorial-modeling-and-antioxidant-activities-of-zingiberaceae-family-rhizomes
#11
Talambedu Usha, Sushen Pradhan, Arvind Kumar Goyal, Shanmugarajan Dhivya, H P Prashanth Kumar, Manoj Kumar Singh, Neelu Joshi, Bharat Chandra Basistha, K R Siddalinga Murthy, Saravanakumar Selvaraj, Sushil Kumar Middha
Objective: The main aim of this scientific report was to investigate a series of phytochemicals in silico and the pharmacology of four plants found at higher altitude in the ginger family, Zingiberaceae (incl. Costaceae) from North-East India, particularly Sikkim. First, the goal was to determine the biological activities of the four herbs (used under Zingiberaceae family) using antioxidant assays to identify the best species. Second, previously reported compounds in litero were subsequently screened for their anticancerous activities using in silico methods...
October 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/29140595/modulation-of-quorum-sensing-in-a-gram-positive-pathogen-by-linear-imprinted-copolymers-with-anti-infective-properties
#12
Anfal Motib, Antonio Guerreiro, Firas Al-Bayati, Elena Piletska, Irfan Manzoor, Sulman Shafeeq, Anagha Kadam, Oscar Kuipers, Luisa Hiller, Todd Cowen, Sergey Piletsky, Peter Andrew, Hasan Yesilkaya
Here we describe the development, characterization and biological testing of a new type of linear molecularly imprinted polymer (LMIP) designed to act as anti-infective by blocking the quorum sensing (QS) mechanism and so preventing virulence of the pathogen Streptococcus pneumoniae. The LMIP is prepared (polymerized) in presence of a template molecule, but unlike in traditional molecular imprinting approaches no cross-linker is used. This results in soluble low molecular weight polymer that can act as drug agent in vitro and in vivo...
November 15, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/29140409/ebolavirus-interferon-antagonists-protein-interaction-perspectives-to-combat-pathogenesis
#13
Anupam Banerjee, Abantika Pal, Debnath Pal, Pralay Mitra
Zaire ebolavirus, one of the most pathogenic species of Ebolavirus, is a significant threat to the human community being both highly infectious and lethal. The viral proteins (VPs), specifically VP24 and VP35, antagonize the interferon (IFN) proteins accountable for human immune response. Several efforts have been made to design vaccines and therapeutics drugs. However, the success is not encouraging because of limited knowledge about the binding site information of the VPs. Such limitations stem largely from the highly infectious nature of the virus that requires specialized personnel and biosafety laboratories...
November 13, 2017: Briefings in Functional Genomics
https://www.readbyqxmd.com/read/29139324/molecular-dynamics-simulations-and-novel-drug-discovery
#14
Xuewei Liu, Danfeng Shi, Shuangyan Zhou, Hongli Liu, Huanxiang Liu, Xiaojun Yao
Molecular dynamics (MD) simulations can provide not only plentiful dynamical structural information on biomacromolecules but also a wealth of energetic information about protein and ligand interactions. Such information is very important to understanding the structure-function relationship of the target and the essence of protein-ligand interactions and to guiding the drug discovery and design process. Thus, MD simulations have been applied widely and successfully in each step of modern drug discovery. Areas covered: In this review, the authors review the applications of MD simulations in novel drug discovery, including the pathogenic mechanisms of amyloidosis diseases, virtual screening and the interaction mechanisms between drugs and targets...
November 15, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/29137527/binding-modes-of-bcl-2-homology-3-bh3-peptides-with-anti-apoptotic-protein-a1-and-redesign-of-peptide-inhibitors-a-computational-study
#15
Yantao Chen, Jun Wang, Jian Zhang, Wei Wang
The interaction between protein and peptide ligand is a challenging problem in molecular biology and drug design. The binding of the Bcl-2 homology 3 (BH3) peptide to the anti-apoptotic protein A1 was revealed as a critical step in the regulation of apoptosis. These BH3 peptides hold high structural similarity, but are diverse in their regulation abilities. Based on molecular simulations and MM-P(G)BSA methods, this work presented a detailed analysis on binding mechanism of the BH3 peptides derived from PUMA and BMF...
November 15, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/29136213/knottin-the-database-of-inhibitor-cystine-knot-scaffold-after-10-years-toward-a-systematic-structure-modeling
#16
Guillaume Postic, Jérôme Gracy, Charlotte Périn, Laurent Chiche, Jean-Christophe Gelly
Knottins, or inhibitor cystine knots (ICKs), are ultra-stable miniproteins with multiple applications in drug design and medical imaging. These widespread and functionally diverse proteins are characterized by the presence of three interwoven disulfide bridges in their structure, which form a unique pseudoknot. Since 2004, the KNOTTIN database (www.dsimb.inserm.fr/KNOTTIN/) has been gathering standardized information about knottin sequences, structures, functions and evolution. The website also provides access to bibliographic data and to computational tools that have been specifically developed for ICKs...
November 9, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29134510/drug-design-for-alk-positive-nsclc-an-integrated-pharmacophore-based-3d-qsar-and-virtual-screening-strategy
#17
Nivya James, V Shanthi, K Ramanathan
The increasing death rates related to anaplastic lymphoma kinase (ALK)-positive lung cancer culminated in a significant interest in the discovery of novel inhibitors for ALK. In the present research work, pharmacophore-based 3D QSAR modeling and virtual screening strategy have been carried out to address these issues. Initially, a five-point pharmacophore model was developed using the biological data of 50 compounds which includes an FDA-approved ALK inhibitor, crizotinib. Using the generated pharmacophore, a 3D QSAR model was developed and used as a query to screen the DrugBank database...
November 13, 2017: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/29134431/impact-of-domain-knowledge-on-blinded-predictions-of-binding-energies-by-alchemical-free-energy-calculations
#18
Antonia S J S Mey, Jordi Juárez Jiménez, Julien Michel
The Drug Design Data Resource (D3R) consortium organises blinded challenges to address the latest advances in computational methods for ligand pose prediction, affinity ranking, and free energy calculations. Within the context of the second D3R Grand Challenge several blinded binding free energies predictions were made for two congeneric series of Farsenoid X Receptor (FXR) inhibitors with a semi-automated alchemical free energy calculation workflow featuring FESetup and SOMD software tools. Reasonable performance was observed in retrospective analyses of literature datasets...
November 13, 2017: Journal of Computer-aided Molecular Design
https://www.readbyqxmd.com/read/29134430/modern-drug-design-the-implication-of-using-artificial-neuronal-networks-and-multiple-molecular-dynamic-simulations
#19
Oleksandr Yakovenko, Steven J M Jones
We report the implementation of molecular modeling approaches developed as a part of the 2016 Grand Challenge 2, the blinded competition of computer aided drug design technologies held by the D3R Drug Design Data Resource ( https://drugdesigndata.org/ ). The challenge was focused on the ligands of the farnesoid X receptor (FXR), a highly flexible nuclear receptor of the cholesterol derivative chenodeoxycholic acid. FXR is considered an important therapeutic target for metabolic, inflammatory, bowel and obesity related diseases (Expert Opin Drug Metab Toxicol 4:523-532, 2015), but in the context of this competition it is also interesting due to the significant ligand-induced conformational changes displayed by the protein...
November 13, 2017: Journal of Computer-aided Molecular Design
https://www.readbyqxmd.com/read/29133831/protein-ligand-blind-docking-using-quickvina-w-with-inter-process-spatio-temporal-integration
#20
Nafisa M Hassan, Amr A Alhossary, Yuguang Mu, Chee-Keong Kwoh
"Virtual Screening" is a common step of in silico drug design, where researchers screen a large library of small molecules (ligands) for interesting hits, in a process known as "Docking". However, docking is a computationally intensive and time-consuming process, usually restricted to small size binding sites (pockets) and small number of interacting residues. When the target site is not known (blind docking), researchers split the docking box into multiple boxes, or repeat the search several times using different seeds, and then merge the results manually...
November 13, 2017: Scientific Reports
keyword
keyword
84853
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"