Search results for "Molecular dynamic"

Sulfonamide moiety as "molecular chimera" in the design of new drugs.

2021

Background: The -SO2NH- group is of great significance in modern pharmaceutical use since, in sulfa-drugs, it is possible to introduce easily chemical modifications, and even small changes may lead to an improved version of an already existing drug. Objective: This paper aims to describe updated information in the sulfonamide field with a particular focus on new mechanisms of action, especially if discovered by employing computational approaches. Methods: Research articles that focused on the use of the sulfonamide moiety for the design, synthesis, and in vitro/in vivo tests of various diseases were collected from various search engines like PubMed, Science Direct, Google Scholar, and Scop…

CO(2)-water supercritical mixtures: Test of a potential model against neutron diffraction data

2007

Abstract A neutron diffraction experiment on supercritical mixtures of water and CO 2 at two concentrations is presented. Data are analyzed within the EPSR framework and the water–water and water–CO 2 radial distribution functions are compared with those calculated by a Molecular Dynamics simulation performed by using the TIPS2 and EPM-M potential models for water and CO 2 respectively. It is found that the Molecular Dynamics simulation reproduces the overall shape of the site–site radial distribution functions, although missing a few subtle changes brought along when the CO 2 concentration is increased.

Synthesis and Structure-Affinity Relationships of Spirocyclic Benzopyrans with Exocyclic Amino Moiety

2019

σ1 and/or σ2 receptors play a crucial role in pathological conditions such as pain, neurodegenerative disorders, and cancer. A set of spirocyclic cyclohexanes with diverse O-heterocycles and amino moieties (general structure III) was prepared and pharmacologically evaluated. In structure-activity relationships studies, the σ1 receptor affinity and σ1:σ2 selectivity were correlated with the stereochemistry, the kind and substitution pattern of the O-heterocycle, and the substituents at the exocyclic amino moiety. cis-configured 2-benzopyran cis-11b bearing a methoxy group and a tertiary cyclohexylmethylamino moiety showed the highest σ1 affinity ( Ki = 1.9 nM) of this series of compounds. In…

Force Distribution Analysis of Mechanochemically Reactive Dimethylcyclobutene

2013

Internal molecular forces can guide chemical reactions, yet are not straightforwardly accessible within a quantum mechanical description of the reacting molecules. Here, we present a force-matching force distribution analysis (FM-FDA) to analyze internal forces in molecules. We simulated the ring opening of trans-3,4-dimethylcyclobutene (tDCB) with on-the-fly semiempirical molecular dynamics. The self-consistent density functional tight binding (SCC-DFTB) method accurately described the force-dependent ring-opening kinetics of tDCB, showing quantitative agreement with both experimental and computational data at higher levels. Mechanical force was applied in two different ways, namely, exter…

Consensus modelling and molecular dynamics studies for the identification of novel telomerase inhibitors as anti-cancer agents

2018

Telomerase plays an important role in early stages of life-maintaing telomere and chromosomal integrity of frequently dividing cells. It turns dormant in most somatic cells during adulthood. However, in cancer cells, telomerase gets reactivated and works tirelessly to maintain the length of telomeres, leading to immortality of cells. Hence, in this study, we have used a combined ligand-based and structure based drug design approach for the identification of novel telomerase inhibitors as anti-cancer agents. We have generated ligand-based QSAR models and structure-based pharmacophores models, according our recent MYSHAPE approach (1), and validated exhaustively. The validated models were use…

Effect of ligand-binding on protein function

2014

Rational drug discovery : structural studies of protein-ligand complexes

2011

Structure and dynamics in liquid bismuth and Bin clusters: A density functional study

2014

Density functional/molecular dynamics simulations with more than 500 atoms have been performed on liquid bismuth at 573, 773, 923, and 1023 K and on neutral Bi clusters with up to 14 atoms. There are similar structural patterns (coordination numbers, bond angles, and ring patterns) in the liquid and the clusters, with significant differences from the rhombohedral crystalline form. We study the details of the structure (structure factor, pair, and cavity distribution functions) and dynamical properties (vibration frequencies, diffusion constants, power spectra), and compare with experimental results where available. While the three short covalent bonds typical to pnictogens are characteristi…

Molecular Basis of SARS-CoV-2 Nsp1-Induced Immune Translational Shutdown as Revealed by All-Atom Simulations.

2021

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic represents the most severe global health crisis in modern human history. One of the major SARS-CoV-2 virulence factors is nonstructural protein 1 (Nsp1), which, outcompeting with the binding of host mRNA to the human ribosome, triggers a translation shutdown of the host immune system. Here, microsecond-long all-atom simulations of the C-terminal portion of the SARS-CoV-2/SARS-CoV Nsp1 in complex with the 40S ribosome disclose that SARS-CoV-2 Nsp1 has evolved from its SARS-CoV ortholog to more effectively hijack the ribosome by undergoing a critical switch of Q/E158 and E/Q159 residues that perfects Nsp1's interactions…

Mechanisms of irreversible aquaporin-10 inhibition by organogold compounds studied by combined biophysical methods and atomistic simulations

2021

Abstract The inhibition of glycerol permeation via human aquaporin-10 (hAQP10) by organometallic gold complexes has been studied by stopped-flow fluorescence spectroscopy, and its mechanism has been described using molecular modelling and atomistic simulations. The most effective hAQP10 inhibitors are cyclometalated Au(III) C^N compounds known to efficiently react with cysteine residues leading to the formation of irreversible C–S bonds. Functional assays also demonstrate the irreversibility of the binding to hAQP10 by the organometallic complexes. The obtained computational results by metadynamics show that the local arylation of Cys209 in hAQP10 by one of the gold inhibitors is mapped int…