Analysis of cause of failure of new targeting peptide in PEGylated liposome: Molecular modeling as rational design tool for nanomedicine

2012 ◽  
Vol 46 (3) ◽  
pp. 121-130 ◽  
Author(s):  
Julia Lehtinen ◽  
Aniket Magarkar ◽  
Michał Stepniewski ◽  
Satu Hakola ◽  
Mathias Bergman ◽  
...  
Keyword(s):  
Molecular Modeling ◽  
Rational Design ◽  
Design Tool ◽  
Pegylated Liposome ◽  
Cause Of Failure ◽  
Targeting Peptide

3D-QSAR Methodologies and Molecular Modeling in Bioinformatics for the Search of Novel Anti-HIV Therapies: Rational Design of Entry Inhibitors

2013 ◽  
Vol 8 (4) ◽  
pp. 452-464 ◽  
Author(s):  
Alejandro Speck-Planche ◽  
Valeria Kleandrova ◽  
Marcus Scotti ◽  
M. Cordeiro
Keyword(s):  
Molecular Modeling ◽  
Rational Design ◽  
3D Qsar ◽  
Entry Inhibitors ◽  
Anti Hiv

scholarly journals Polymeric micelles and molecular modeling applied to the development of radiopharmaceuticals

2012 ◽  
Vol 48 (1) ◽  
pp. 1-16 ◽  
Author(s):  
Sibila Roberta Marques Grallert ◽  
Carlota de Oliveira Rangel-Yagui ◽  
Kerly Fernanda Mesquita Pasqualoto ◽  
Leoberto Costa Tavares
Keyword(s):  
Molecular Modeling ◽  
Rational Design ◽  
Polymeric Micelles ◽  
Single Photon ◽  
Photon Emission ◽  
Disease Process ◽  
Diagnostic Techniques ◽  
Emission Computed Tomography ◽  
Amphiphilic Copolymers ◽  
Design Strategies

Micelles composed of amphiphilic copolymers linked to a radioactive element are used in nuclear medicine predominantly as a diagnostic application. A relevant advantage of polymeric micelles in aqueous solution is their resulting particle size, which can vary from 10 to 100 nm in diameter. In this review, polymeric micelles labeled with radioisotopes including technetium (99mTc) and indium (111In), and their clinical applications for several diagnostic techniques, such as single photon emission computed tomography (SPECT), gamma-scintigraphy, and nuclear magnetic resonance (NMR), were discussed. Also, micelle use primarily for the diagnosis of lymphatic ducts and sentinel lymph nodes received special attention. Notably, the employment of these diagnostic techniques can be considered a significant tool for functionally exploring body systems as well as investigating molecular pathways involved in the disease process. The use of molecular modeling methodologies and computer-aided drug design strategies can also yield valuable information for the rational design and development of novel radiopharmaceuticals.

scholarly journals Design, Synthesis and Molecular Modeling Study of Conjugates of ADP and Morpholino Nucleosides as A Novel Class of Inhibitors of PARP-1, PARP-2 and PARP-3

2019 ◽  
Vol 21 (1) ◽  
pp. 214
Author(s):  
Yuliya V. Sherstyuk ◽  
Nikita V. Ivanisenko ◽  
Alexandra L. Zakharenko ◽  
Maria V. Sukhanova ◽  
Roman Y. Peshkov ◽  
...  
Keyword(s):  
Molecular Modeling ◽  
Binding Site ◽  
Rational Design ◽  
In Silico Analysis ◽  
Parp Inhibition ◽  
High Yield ◽  
Design Synthesis ◽  
Molecular Modeling Study ◽  
Parp 1 ◽  
Modeling Study

We report on the design, synthesis and molecular modeling study of conjugates of adenosine diphosphate (ADP) and morpholino nucleosides as potential selective inhibitors of poly(ADP-ribose)polymerases-1, 2 and 3. Sixteen dinucleoside pyrophosphates containing natural heterocyclic bases as well as 5-haloganeted pyrimidines, and mimicking a main substrate of these enzymes, nicotinamide adenine dinucleotide (NAD+)-molecule, have been synthesized in a high yield. Morpholino nucleosides have been tethered to the β-phosphate of ADP via a phosphoester or phosphoramide bond. Screening of the inhibiting properties of these derivatives on the autopoly(ADP-ribosyl)ation of PARP-1 and PARP-2 has shown that the effect depends upon the type of nucleobase as well as on the linkage between ADP and morpholino nucleoside. The 5-iodination of uracil and the introduction of the P–N bond in NAD+-mimetics have shown to increase inhibition properties. Structural modeling suggested that the P–N bond can stabilize the pyrophosphate group in active conformation due to the formation of an intramolecular hydrogen bond. The most active NAD+ analog against PARP-1 contained 5-iodouracil 2ʹ-aminomethylmorpholino nucleoside with IC50 126 ± 6 μM, while in the case of PARP-2 it was adenine 2ʹ-aminomethylmorpholino nucleoside (IC50 63 ± 10 μM). In silico analysis revealed that thymine and uracil-based NAD+ analogs were recognized as the NAD+-analog that targets the nicotinamide binding site. On the contrary, the adenine 2ʹ-aminomethylmorpholino nucleoside-based NAD+ analogs were predicted to identify as PAR-analogs that target the acceptor binding site of PARP-2, representing a novel molecular mechanism for selective PARP inhibition. This discovery opens a new avenue for the rational design of PARP-1/2 specific inhibitors.

Quantitative analysis of debris torrent hazards for design of remedial measures

1984 ◽  
Vol 21 (4) ◽  
pp. 663-677 ◽  
Author(s):  
O. Hungr ◽  
G. C. Morgan ◽  
R. Kellerhals
Keyword(s):  
Rational Design ◽  
Design Tool ◽  
Provincial Government ◽  
Remedial Measures ◽  
Runout Distance ◽  
Organic Debris ◽  
Discharge Velocity ◽  
Frequency Peak ◽  
Retention Barriers ◽  
Run Up

Debris torrents, which are rapid flows of soil and organic debris down steep mountain channels, are a major natural hazard in many parts of British Columbia.A series of recent occurrences along the Squamish Highway, north of Vancouver, led the provincial government to initiate a systematic study of debris torrents in this area. This 2 year study involved hazard risk assessment and resulted in the design of a comprehensive system of remedial measures comprising debris retention barriers and basins, channel improvements and diversions, and the reconstruction of bridges. It was necessary in the course of this effort to formulate new design procedures covering the dynamic behaviour of debris torrents, as there was no accepted practical methodology suitable for Western Canadian conditions.This paper provides an approach to determining magnitude (volume of debris material involved), frequency, peak discharge, velocity, conditions for deposition, runout distance, behaviour in bends and run-up against barriers, and dynamic thrust and impact loadings. The procedures are based on some of the more practical concepts available in the specialized literature, supplemented by simple original theories and calibrated against several recent debris torrent events from British Columbia for which sufficiently detailed observational data exists. To be generally applicable, the procedures require a wider and more thorough calibration. They are presented here as working hypotheses that can be used as a guide to the assembly of additional data and provide a rational design tool to supplement the application of experience and judgement. Key words: debris torrents, debris flows, slope hazards, landslide dynamics, remedial measures, engineering design.

scholarly journals Molecular Modeling Combined with Advanced Chemistry for the Rational Design of Efficient Graphene Dispersing Agents

2015 ◽  
Vol 5 (1) ◽  
pp. 24-29 ◽  
Author(s):  
Konstantinia D. Papadimitriou ◽  
Emmanuel N. Skountzos ◽  
Sandra S. Gkermpoura ◽  
Ioannis Polyzos ◽  
Vlasis G. Mavrantzas ◽  
...  
Keyword(s):  
Molecular Modeling ◽  
Rational Design ◽  
Dispersing Agents

Optimization of Offshore Structures Based on Linear Analysis of Wave-Body Interaction

2008 ◽  
Author(s):  
Lothar Birk ◽  
Gu¨nther F. Clauss
Keyword(s):  
Rational Design ◽  
User Interaction ◽  
Offshore Structures ◽  
Design Tool ◽  
Integrated System ◽  
Diffraction Radiation ◽  
Hydrodynamic Analysis ◽  
Automated Generation ◽  
Wide Range ◽  
Hull Design

This paper discusses new developments in automated hull shape optimization spearheaded by the authors. The use of the linear diffraction-radiation panel code WAMIT® as a design tool is highlighted. Early optimization results yielded bodies with extreme shapes. A series of studies has been performed comparing model test data and numerical computations. The presented comparisons reinforce the numerical results. The authors connected the reliable hydrodynamic analysis provided by WAMIT® with a newly developed parametric hull design methodology. This allows the automated generation of hull shapes without requiring user interaction. Single- and multi-objective optimization algorithms are available to solve a wide range of nonlinear programming problems. The integrated system optimizes hulls by minimizing motions and forces in waves. This is especially important for innovative systems when prior design experience is missing. The results of an optimization run provide a wealth of information which can be utilized to support rational design decisions.

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