Search results for "Rational design"
showing 10 items of 63 documents
Rational Synthesis of Chiral Metal-Organic Frameworks from Preformed Rodlike Secondary Building Units.
2017
The lack of rational design methodologies to obtain chiral rod-based MOFs is a current synthetic limitation that hampers further expansion of MOF chemistry. Here we report a metalloligand design strategy consisting of the use, for the first time, of preformed 1D rodlike SBUs (1) for the rational preparation of a chiral 3D MOF (2) exhibiting a rare eta net topology. The encoded chiral information on the enantiopure ligand is efficiently transmitted first to the preformed helical 1D building block and, in a second stage, to the resulting chiral 3D MOF. These results open new routes for the rational design of chiral rod-based MOFs, expanding the scope of these unique porous materials.
Fifteen operationally important decisions in the planning of biodiversity offsets
2018
Many development projects, whether they are about construction of factories, mines, roads, railways, new suburbs, shopping malls, or even individual houses, have negative environmental consequences. Biodiversity offsetting is about compensating that damage, typically via habitat restoration, land management, or by establishment of new protected areas. Offsets are the fourth step of the so-called mitigation hierarchy, in which ecological damage is first avoided, minimized second, and third restored locally. Whatever residual damage remains is then offset. Offsetting has been increasingly adopted all around the world, but simultaneously serious concerns are expressed about the validity of the…
Molecular basis of SARS-CoV-2 infection and rational design of potential antiviral agents: Modeling and simulation approaches
2020
International audience; The emergence in late 2019 of the coronavirus SARS-CoV-2 has resulted in the breakthrough of the COVID-19 pandemic that is presently affecting a growing number of countries. The development of the pandemic has also prompted an unprecedented effort of the scientific community to understand the molecular bases of the virus infection and to propose rational drug design strategies able to alleviate the serious COVID-19 morbidity. In this context, a strong synergy between the structural biophysics and molecular modeling and simulation communities has emerged, resolving at the atomistic level the crucial protein apparatus of the virus and revealing the dynamic aspects of k…
Nanoscale Engineering of Designer Cellulosomes.
2016
Biocatalysts showcase the upper limit obtainable for high-speed molecular processing and transformation. Efforts to engineer functionality in synthetic nanostructured materials are guided by the increasing knowledge of evolving architectures, which enable controlled molecular motion and precise molecular recognition. The cellulosome is a biological nanomachine, which, as a fundamental component of the plant-digestion machinery from bacterial cells, has a key potential role in the successful development of environmentally-friendly processes to produce biofuels and fine chemicals from the breakdown of biomass waste. Here, the progress toward so-called "designer cellulosomes", which provide an…
An overview of recent molecular dynamics applications as medicinal chemistry tools for the undruggable site challenge
2018
Molecular dynamics (MD) has become increasingly popular due to the development of hardware and software solutions and the improvement in algorithms, which allowed researchers to scale up calculations in order to speed them up. MD simulations are usually used to address protein folding issues or protein-ligand complex stability through energy profile analysis over time. In recent years, the development of new tools able to deeply explore a potential energy surface (PES) has allowed researchers to focus on the dynamic nature of the binding recognition process and binding-induced protein conformational changes. Moreover, modern approaches have been demonstrated to be effective and reliable in …
Discovery and Biological Evaluation of Potent and Selective N-Methylene Saccharin-Derived Inhibitors for Rhomboid Intramembrane Proteases
2017
Rhomboids are intramembrane serine proteases and belong to the group of structurally and biochemically most comprehensively characterized membrane proteins. They are highly conserved and ubiquitously distributed in all kingdoms of life and function in a wide range of biological processes, including epidermal growth factor signaling, mitochondrial dynamics, and apoptosis. Importantly, rhomboids have been associated with multiple diseases, including Parkinson's disease, type 2 diabetes, and malaria. However, despite a thorough understanding of many structural and functional aspects of rhomboids, potent and selective inhibitors of these intramembrane proteases are still not available. In this …
Large strain stimulation promotes extracellular matrix production and stiffness in an elastomeric scaffold model
2016
Mechanical conditioning of engineered tissue constructs is widely recognized as one of the most relevant methods to enhance tissue accretion and microstructure, leading to improved mechanical behaviors. The understanding of the underlying mechanisms remains rather limited, restricting the development of in silico models of these phenomena, and the translation of engineered tissues into clinical application. In the present study, we examined the role of large strip-biaxial strains (up to 50%) on ECM synthesis by vascular smooth muscle cells (VSMCs) micro-integrated into electrospun polyester urethane urea (PEUU) constructs over the course of 3 weeks. Experimental results indicated that VSMC …
Additives for vaccine storage to improve thermal stability of adenoviruses from hours to months
2016
Up to 80% of the cost of vaccination programmes is due to the cold chain problem (that is, keeping vaccines cold). Inexpensive, biocompatible additives to slow down the degradation of virus particles would address the problem. Here we propose and characterize additives that, already at very low concentrations, improve the storage time of adenovirus type 5. Anionic gold nanoparticles (10−8–10−6 M) or polyethylene glycol (PEG, molecular weight ∼8,000 Da, 10−7–10−4 M) increase the half-life of a green fluorescent protein expressing adenovirus from ∼48 h to 21 days at 37 °C (from 7 to >30 days at room temperature). They replicate the known stabilizing effect of sucrose, but at several orders of…
Hydrogen Bond Fluctuations Control Photochromism in a Reversibly Photo-Switchable Fluorescent Protein
2015
Reversibly switchable fluorescent proteins (RSFPs) are essential for high-resolution microscopy of biological samples, but the reason why these proteins are photochromic is still poorly understood. To address this problem, we performed molecular dynamics simulations of the fast switching Met159Thr mutant of the RSFP Dronpa. Our simulations revealed a ground state structural heterogeneity in the chromophore pocket that consists of three populations with one, two, or three hydrogen bonds to the phenolate moiety of the chromophore. By means of non-adiabatic quantum mechanics/molecular dynamics simulations, we demonstrated that the subpopulation with a single hydrogen bond is responsible for of…
Interaction between odorants and proteins involved in the perception of smell: the case of odorant-binding proteins probed by molecular modelling and…
2012
A joint approach that combines molecular modelling and fluorescence spectroscopy is used to study the affinity of an odorant binding protein towards various odorant molecules. We focus on the capability of molecular modelling to rank odorants according to their affinity with this protein, which is involved in the sense of smell. Although ligand-based approaches are unable to propose an accurate model attending to the strength of the bond with the odorant-binding protein, receptor-based structures considering either static or dynamic structure of the protein perform equally to discriminate between good, medium and low affinity odorants. Such approaches will be useful for further rational des…