Search results for "Simulation"

All-atom simulations to studying metallodrugs/target interactions.

2021

Abstract Metallodrugs are extensively used to treat and diagnose distinct disease types. The unique physical–chemical properties of metal ions offer tantalizing opportunities to tailor effective scaffolds for selectively targeting specific biomolecules. Modern experimental techniques have collected a large body of structural data concerning the interactions of metallodrugs with their biomolecular targets, although being unable to exhaustively assess the molecular basis of their mechanism of action. In this scenario, the complementary use of accurate computational methods allows uncovering the minutiae of metallodrugs/targets interactions and their underlying mechanism of action at an atomic…

Spectral entropy based neuronal network synchronization analysis based on microelectrode array measurements

2016

Synchrony and asynchrony are essential aspects of the functioning of interconnected neuronal cells and networks. New information on neuronal synchronization can be expected to aid in understanding these systems. Synchronization provides insight in the functional connectivity and the spatial distribution of the information processing in the networks. Synchronization is generally studied with time domain analysis of neuronal events, or using direct frequency spectrum analysis, e.g., in specific frequency bands. However, these methods have their pitfalls. Thus, we have previously proposed a method to analyze temporal changes in the complexity of the frequency of signals originating from differ…

2019

As rats learn to search for multiple sources of food or water in a complex environment, they generate increasingly efficient trajectories between reward sites. Such spatial navigation capacity involves the replay of hippocampal place-cells during awake states, generating small sequences of spatially related place-cell activity that we call "snippets". These snippets occur primarily during sharp-wave-ripples (SWRs). Here we focus on the role of such replay events, as the animal is learning a traveling salesperson task (TSP) across multiple trials. We hypothesize that snippet replay generates synthetic data that can substantially expand and restructure the experience available and make learni…

SpCLUST: Towards a fast and reliable clustering for potentially divergent biological sequences

2019

International audience; This paper presents SpCLUST, a new C++ package that takes a list of sequences as input, aligns them with MUSCLE, computes their similarity matrix in parallel and then performs the clustering. SpCLUST extends a previously released software by integrating additional scoring matrices which enables it to cover the clustering of amino-acid sequences. The similarity matrix is now computed in parallel according to the master/slave distributed architecture, using MPI. Performance analysis, realized on two real datasets of 100 nucleotide sequences and 1049 amino-acids ones, show that the resulting library substantially outperforms the original Python package. The proposed pac…

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…

In silico drug discovery of major metabolites from spices as SARS-CoV-2 main protease inhibitors

2020

Coronavirus Disease 2019 (COVID-19) is an infectious illness caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), originally identified in Wuhan, China (December 2019) and has since expanded into a pandemic. Here, we investigate metabolites present in several common spices as possible inhibitors of COVID-19. Specifically, 32 compounds isolated from 14 cooking seasonings were examined as inhibitors for SARS-CoV-2 main protease (Mpro), which is required for viral multiplication. Using a drug discovery approach to identify possible antiviral leads, in silico molecular docking studies were performed. Docking calculations revealed a high potency of salvianolic acid A and curcu…

Reactome graph database: Efficient access to complex pathway data

2018

Reactome is a free, open-source, open-data, curated and peer-reviewed knowledgebase of biomolecular pathways. One of its main priorities is to provide easy and efficient access to its high quality curated data. At present, biological pathway databases typically store their contents in relational databases. This limits access efficiency because there are performance issues associated with queries traversing highly interconnected data. The same data in a graph database can be queried more efficiently. Here we present the rationale behind the adoption of a graph database (Neo4j) as well as the new ContentService (REST API) that provides access to these data. The Neo4j graph database and its qu…

Measuring spectrally-resolved information transfer.

2020

Information transfer, measured by transfer entropy, is a key component of distributed computation. It is therefore important to understand the pattern of information transfer in order to unravel the distributed computational algorithms of a system. Since in many natural systems distributed computation is thought to rely on rhythmic processes a frequency resolved measure of information transfer is highly desirable. Here, we present a novel algorithm, and its efficient implementation, to identify separately frequencies sending and receiving information in a network. Our approach relies on the invertible maximum overlap discrete wavelet transform (MODWT) for the creation of surrogate data in t…

Design, synthesis and preliminary evaluation of dopamine-amino acid conjugates as potential D1 dopaminergic modulators.

2016

Abstract The dopamine-amino acid conjugate DA-Phen was firstly designed to obtain a useful prodrug for the therapy of Parkinson's disease, but experimental evidence shows that it effectively interacts with D1 dopamine receptors (D1DRs), leading to an enhancement in cognitive flexibility and to the development of adaptive strategies in aversive mazes, together with a decrease in despair-like behavior. In this paper, homology modelling, molecular dynamics, and site mapping of D1 receptor were carried out with the aim of further performing docking studies on other dopamine conjugates compared with D1 agonists, in the attempt to identify new compounds with potential dopaminergic activity. Two n…

Reversal of multidrug resistance by Marsdenia tenacissima and its main active ingredients polyoxypregnanes.

2016

Abstract Ethnopharmacological relevance Multidrug resistance (MDR) of cancer is often associated with the overexpression of ATP-binding cassette (ABC) transporters, such as P-glycoprotein (P-gp), multidrug resistance-associated protein-1 (MRP-1) and breast cancer resistance protein (BCRP or ABCG2), in cancer cells, which facilitates the active efflux of a wide variety of chemotherapeutic drugs out of the cells. Marsdenia tenacissima is a traditional Chinese medicinal herb that has long been clinically used for treatment of cancers, particularly in combinational use with anticancer drugs. Polyoxypregnanes (POPs) are identified as main constituents of this herb, and three of them have been re…