Search results for "Molecular Dynamic"

The Photocycle of Bacteriophytochrome Is Initiated by Counterclockwise Chromophore Isomerization.

2022

Photoactivation of bacteriophytochrome involves a cis–trans photoisomerization of a biliverdin chromophore, but neither the precise sequence of events nor the direction of the isomerization is known. Here, we used nonadiabatic molecular dynamics simulations on the photosensory protein dimer to resolve the isomerization mechanism in atomic detail. In our simulations the photoisomerization of the D ring occurs in the counterclockwise direction. On a subpicosecond time scale, the photoexcited chromophore adopts a short-lived intermediate with a highly twisted configuration stabilized by an extended hydrogen-bonding network. Within tens of picoseconds, these hydrogen bonds break, allowing the c…

Human DNA Telomeres in Presence of Oxidative Lesions: The Crucial Role of Electrostatic Interactions on the Stability of Guanine Quadruplexes

2019

By using all atom molecular dynamics simulations, we studied the behavior of human DNA telomere sequences in guanine quadruplex (G4) conformation and in the presence of oxidative lesions, namely abasic sites. In particular, we evidenced that while removing one guanine base induces a significant alteration and destabilization of the involved leaflet, human telomere oligomers tend, in most cases, to maintain at least a partial quadruplex structure, eventually by replacing the empty site with undamaged guanines of different leaflets. This study shows that (i) the disruption of the quadruplex leaflets induces the release of at least one of the potassium cations embedded in the quadruplex channe…

Elucidating the ligand shell structure and dynamics of Au683MBA32 gold nanocluster using molecular dynamics simulations

2017

Synthesising novel gold nanoparticles and -clusters can be often easier than characterising them, and after experimental analysis many options for the possible molecular formula of the cluster may remain as equally valid options. These options may be investigated by quantum computational means, such as density functional theory, but since DFT includes the electronic interactions, this might take time and excessive effort if the amount of options is large. In this thesis a new way of easing the computational task is introduced by a novel method, that combines a guessing algorithm and molecular dynamics simulations. The algorithm produces possible structures by utilising existing structures o…

Virtual screening : development of a novel structure-based method

2013

The electric properties of ionic solutions: a molecular dynamics (preliminary) study

2011

Best Practices in Constant pH MD Simulations: Accuracy and Sampling

2022

Various approaches have been proposed to include the effect of pH in molecular dynamics (MD) simulations. Among these, the λ-dynamics approach proposed by Brooks and co-workers [Kong, X.; Brooks III, C. L. J. Chem. Phys.1996, 105, 2414−2423] can be performed with little computational overhead and hfor each typeence be used to routinely perform MD simulations at microsecond time scales, as shown in the accompanying paper [Aho, N. et al. J. Chem. Theory Comput.2022, DOI: 10.1021/acs.jctc.2c00516]. At such time scales, however, the accuracy of the molecular mechanics force field and the parametrization becomes critical. Here, we address these issues and provide the community with guidelines on…

Molecular dynamics simulations of heavy ion induced defects in SiC Schottky diodes

2018

Heavy ion irradiation increases the leakage current in reverse-biased SiC Schottky diodes. This letter demonstrates, via molecular dynamics simulations, that a combination of bias and ion-deposited energy is required to produce the degradation. Peer reviewed

MOLECULAR DYNAMICS AND DOCKING IN THE STUDY OF NEW INHIBITORS OF MDM2-p53 INTERACTION

2008

Targeting Orthosteric and Allosteric Pockets of Aromatase via Dual-Mode Novel Azole Inhibitors

2020

[Image: see text] Breast cancer (BC) is the most diffused cancer type in women and the second leading cause of death among the female population. Effective strategies to fight estrogen responsive (ER+) BC, which represents 70% of all BC cases, rely on estrogen deprivation, via the inhibition of the aromatase enzyme, or the modulation of its cognate estrogen receptor. Current clinical therapies significantly increased patient survival time. Nevertheless, the onset of resistance in metastatic BC patients undergoing prolonged treatments is becoming a current clinical challenge, urgently demanding to devise innovative strategies. In this context, here we designed, synthesized, and performed in …

Structural, Thermodynamic, and Kinetic Traits of Antiestrogen-Compounds Selectively Targeting the Y537S Mutant Estrogen Receptor α Transcriptional Ac…

2019

The most frequently diagnosed cancers in women are the estrogen receptor (ER)-positive breast cancer subtypes, which are characterized by estrogen dependency for their growth. The mainstay of clinical treatment for this tumor relies on the modulation of ER action or on the suppression of estrogen biosynthesis via the administration of Selective ERα Modulators/Down-regulators (SERMs/SERDs) or aromatase inhibitors, respectively. Nevertheless, de novo and acquired resistance to these therapies frequently occurs and represents a major clinical concern for patient survival. Recently, somatic mutations affecting the hormone-binding domain of ERα (i. e. Y537S, Y537N, D538G) have been associated w…