Molecular modelling studies of binding of DACD derivatives into G-Quadruplex DNA: comparison of force field and quantum polarized ligand docking methods

The DNA G-qadruplexes are one of the targets being actively explored for anti-cancer therapy by inhibiting them through small molecules. This computational study was conducted to predict the binding strengths and orientations of a set of novel dimethyl-amino-ethyl-acridine (DACA) analogues that are designed and synthesized in our laboratory, but did not diffract in Synchrotron light.Thecrystal structure of DNA G-Quadruplex(TGGGGT)4(PDB: 1O0K) was used as target for their binding properties in our studies.We used both the force field (FF) and QM/MM derived atomic charge schemes simultaneously for comparing the predictions of drug binding modes and their energetics. This study evaluates the comparative performance of fixed point charge based Glide XP docking and the quantum polarized ligand docking schemes. These results will provide insights on the effects of including or ignoring the drug-receptor interfacial polarization events in molecular docking simulations, which in turn, will aid the rational selection of computational methods at different levels of theory in future drug design programs. Plenty of molecular modelling tools and methods currently exist for modelling drug-receptor or protein-protein, or DNA-protein interactionssat different levels of complexities.Yet, the capasity of such tools to describevarious physico-chemical propertiesmore accuratelyis the next step ahead in currentresearch.Especially, the usage of most accurate methods in quantum mechanics(QM) is severely restricted by theirtedious nature. Though the usage of massively parallel super computing environments resulted in a tremendous improvement in molecular mechanics (MM) calculations like molecular dynamics,they are still capable of dealing with only a couple of tens to hundreds of atoms for QM methods. One such efficient strategy that utilizes thepowers of both MM and QM are the QM/MM hybrid methods. Lately, attempts have been directed towards the goal of deploying several different QM methods for betterment of force field based simulations, but with practical restrictions in place. One of such methods utilizes the inclusion of charge polarization events at the drug-receptor interface, that is not explicitly present in the MM FF.

Progress report from the strategic sanctuary for the destruction of free will

Progress Report from the Strategic Sanctuary for the Destruction of Free Will presents a new work combining film, music and installation that juxtaposes the setting of the institution with the aesthetics of psychedelia.Progress Report from the Strategic Sanctuary for the Destruction of Free Will is an installation, film and sound work that takes over the gallery. Using plain white card, it distorts the structure of the gallery’s architecture, producing a paranoid shrunken space. Inside this space, performers in cardboard costumes re-enact abstracted, broken gestures drawn from video documentation of acid trips, psychedelic dancing, rehab sessions and radical psychotherapy workshops. Progress Report from the Strategic Sanctuary for the Destruction of Free Will has been formed through Pil and Galia Kollectiv’s research into the anti-psychiatry movement, their interests in counter cultural movements and their studies around biopolitics and the proliferation of societal medication. In 1958, having had a life changing experience with LSD, former alcoholic Charles Dederich founded Synanon, a drug rehabilitation program based on residential care and an aggressive form of group therapy called ‘The Game’. The organisation gradually evolved into a controversial alternative community, described in a critical pamphlet as creating Strategic Sanctuaries for the Destruction of Free Will, “a subversive program for mixing delinquents and lefties”. In 1984, anti-psychiatrist R. D. Laing described tranquillizers as chemical straight jackets. With our growing understanding of the plasticity of the brain and the potential to shape it, the tension between liberation and control in the struggle over the mind continues to define our relationship to labour, culture and production. Interrogating these ideas, the exhibition poses the question of whether a collective body can overcome the solipsism of the incommunicable experience of the individual mind.