252 research outputs found
Culture and its perception in strategic alliances, does it affect the performance? An exploratory study into Dutch-German ventures
culture, strategic alliances, performance
CHARMM force field parameterization protocol for self-assembling peptide amphiphiles : the Fmoc moiety
Aromatic peptide amphiphiles are known to self-assemble into nanostructures but the molecular level structure and the mechanism of formation of these nanostructures is not yet understood in detail. Molecular dynamic simulations using the CHARMM force field have been applied to a wide variety of peptide-based systems to obtain molecular level details of processes that are inaccessible with experimental techniques. However, this force field does not include parameters for the aromatic moieties which dictate the self-assembly of these systems. The standard CHARMM force field parameterization protocol uses hydrophilic interactions for the non-bonding parameters evaluation. However, to effectively reproduce the self-assembling behaviour of these molecules, the balance between the hydrophilic and hydrophobic nature of the molecule is essential. In this work, a modified parameterization protocol for the CHARMM force field for these aromatic moieties is presented. This protocol is applied for the specific case of the Fmoc moiety. The resulting set of parameters satisfies the conformational and interactions analysis and is able to reproduce experimental results such as the Fmoc-S-OMe water/octanol partition free energy and the self-assembly of Fmoc-S-OH and Fmoc-Y-OH into spherical micelles and fibres, respectively, while also providing detailed information on the mechanism of these processes. The effectiveness of the parameters for the Fmoc moiety validates the protocol as a robust approach to paramterise this class of compounds
Molecular dynamics simulations reveal disruptive self-assembly in dynamic peptide libraries
There is a significant interest in the use of unmodified self-assembling peptides as building blocks for functional, supramolecular biomaterials. Recently, dynamic peptide libraries (DPLs) have been proposed to select self-assembling materials from dynamically exchanging mixture of dipeptide inputs in the presence of a nonspecific protease enzyme, where peptide sequences are selected and amplified based on their self-assembling tendencies. It was shown that the results of DPL of mixed sequences (e.g. starting from a mixture of dileucine, L2 and diphenylalanine, F2) did not give the same outcome as the separate L2 and F2 libraries (which give rise to formation of F6 and L6), implying that interaction between these sequences could disrupt the self-assembly. In this study, coarse grained molecular dynamic (CG-MD) simulations are used to understand the DPL results for F2, L2 and mixed libraries. CG-MD simulations demonstrate that interactions between precursors can cause the low formation yield of hexapeptides in mixtures of dipeptides and show that this ability to disrupt is influenced by the concentration of the different species in the DPL. The disrupting self-assembly effect between the species in DPL is an important effect to take into account in dynamic combinatorial chemistry as it affects the possible discovery of new materials. The work shows that combined computational and experimental screening can be used complementary and in combination provide a powerful means to discover new supramolecular peptide nanostructures
Managing the strategic process : the impact of national/corporate culture on the strategic behavior of European MNC's
No abstrac
Managing the strategic process : the impact of national/corporate culture on the strategic behavior of European MNC's
No abstrac
Metastable hydrogels from aromatic dipeptides
We demonstrate that the well-known self-assembling dipeptide diphenylalanine (FF) and its amidated derivative (FF-NH2) can form metastable hydrogels upon sonication of the dipeptide solutions. The hydrogels show instantaneous syneresis upon mechanical contact resulting in rapid expulsion of water and collapse into a semi-solid gel
Insight into the esterase like activity demonstrated by an imidazole appended self-assembling hydrogelator
A low molecular weight hydrogelator with a covalently appended imidazole moiety is reported. Capable of percolating water in the pH range of 6 to 8, it proves to be an efficient catalyst upon self-assembly, showing Michaelis-Menten type kinetics. Activities at different pH values correlated with dramatic structural changes were observed. It can hydrolyse p-nitrophenyl acetate (pNPA) as well as inactivated esters, and l and d-phenylalanine methyl esters. The enhanced activity can be related to the conglomeration of catalytic groups upon aggregation resulting in their close proximity and the formation of hydrophobic pockets
Guiding principles for peptide nanotechnology through directed discovery
Life's diverse molecular functions are largely based on only a small number of highly conserved building blocks-the twenty canonical amino acids. These building blocks are chemically simple, but when they are organized in three-dimensional structures of tremendous complexity, new properties emerge. This review explores recent efforts in the directed discovery of functional nanoscale systems and materials based on these same amino acids, but that are not guided by copying or editing biological systems. The review summarises insights obtained using three complementary approaches of searching the sequence space to explore sequence-structure relationships for assembly, reactivity and complexation, namely: (i) strategic editing of short peptide sequences; (ii) computational approaches to predicting and comparing assembly behaviours; (iii) dynamic peptide libraries that explore the free energy landscape. These approaches give rise to guiding principles on controlling order/disorder, complexation and reactivity by peptide sequence design
Short carbohydrate amphiphiles as smart therapeutics targeting cancer
Biocatalytic self-assembly (BSA) emerged as selective and effective approach for cancer therapy. BSA makes use of enzyme-sensitive moiety that is incorporated in an amphiphilic molecule (usually peptide amphiphile, PA). This unit is transfomred/removed upon enzymatic action causing rebalance of the moleculeâ s amphiphilicity and self-assembling ability. Among different enzymes, phosphatases (e.g. alkaline phosphatase, ALP) are the best studied ones for BSA targeting cancer. Recently, we describe a simple carbohydrate amphiphile (CA) as an alternative of PA and demonstrated its potential for treatment of osteosarcoma using BSA. Herein, we discuss another advantage of CAs in cancer therapy: they can act as antagonists of the glucose transporters (GLUTs) due to their structural similarity with glucose. Cancer cells have an accelerated metabolism, which requires high consumption of glucose. As a result, they overexpressed GLUTs, particularly GLUT1 and GLUT3. We studied several cancer cell lines overexpressing GLUTs and demonstrate that indeed the presence of CAs alter the glucose transport: a competitive assay showed that CAs reduced significantly the uptake of glucose, suggesting a possible blocking of GLUTs and glycolysis. Cancer cells cultured in the presence of CAs also showed a decrease in cell proliferation, metabolic activity and activation of an apoptotic pathway, that ultimately led to cell death. We conclude that the selective apoptosis of cancer cells is based on two synergistic mechanisms: formation of pericellular net that traps selectively the phosphatase overexpressing cells and blockage of glucose transport in these cells.info:eu-repo/semantics/publishedVersio
The biological context of HIV-1 host interactions reveals subtle insights into a system hijack
<p>Abstract</p> <p>Background</p> <p>In order to replicate, HIV, like all viruses, needs to invade a host cell and hijack it for its own use, a process that involves multiple protein interactions between virus and host. The HIV-1, Human Protein Interaction Database available at NCBI's website captures this information from the primary literature, containing over 2,500 unique interactions. We investigate the general properties and biological context of these interactions and, thus, explore the molecular specificity of the HIV-host perturbation. In particular, we investigate (i) whether HIV preferentially interacts with highly connected and 'central' proteins, (ii) known phenotypic properties of host proteins inferred from essentiality and disease-association data, and (iii) biological context (molecular function, processes and location) of the host proteins to identify attributes most strongly associated with specific HIV interactions.</p> <p>Results</p> <p>After correcting for ascertainment bias in the literature, we demonstrate a significantly greater propensity for HIV to interact with highly connected and central host proteins. Unexpectedly, we find there are no associations between HIV interaction and inferred essentiality. Similarly, we find a tendency for HIV not to interact with proteins encoded by genes associated with disease. Crucially, we find that functional categories over-represented in HIV-host interactions are innately enriched for highly connected and central proteins in the host system.</p> <p>Conclusions</p> <p>Our results imply that HIV's propensity to interact with highly connected and central proteins is a consequence of interactions with particular cellular functions, rather than being a direct effect of network topological properties. The lack of a propensity for interactions with phenotypically essential proteins suggests a selective pressure to minimise virulence in retroviral evolution. Thus, the specificity of HIV-host interactions is complex, and only superficially explained by network properties.</p
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