Chapter MM-GB(PB)SA Calculations of Protein-Ligand Binding Free Energies

Optical physic

MM-GB(PB)SA Calculations of Protein-Ligand Binding Free Energies

Optical physic

Effects of partial ionization on magnetic flux emergence in the Sun

We have performed 3-D numerical simulations to investigate the effect of partial ionization on the process of magnetic flux emergence. In our study, we have modified the single-fluid MHD equations to include the presence of neutrals and have performed two basic experiments: one that assumes a fully ionized plasma (FI case) and one that assumes a partially ionized plasma (PI case). We find that the PI case brings less dense plasma to and above the solar surface. Furthermore, we find that partial ionization alters the emerging magnetic field structure, leading to a different shape of the polarities in the emerged bipolar regions compared to the FI case. The amount of emerging flux into the solar atmosphere is larger in the PI case, which has the same initial plasma beta as the FI case, but a larger initial magnetic field strength. The expansion of the field above the photosphere occurs relatively earlier in the PI case, and we confirm that the inclusion of partial ionization reduces cooling due to adiabatic expansion. However, it does not appear to work as a heating mechanism for the atmospheric plasma. The performance of these experiments in three dimensions shows that PI does not prevent the formation of unstable magnetic structures, which erupt into the outer solar atmosphere

Toward Rational Design of Selective Molecularly Imprinted Polymers (MIPs) for Proteins: Computational and Experimental Studies of Acrylamide Based Polymers for Myoglobin

Molecularly imprinted polymers (MIPs) have potential as alternatives to antibodies in the diagnosis and treatment of disease. However, atomistic level knowledge of the prepolymerization process is limited that would facilitate rational design of more efficient MIPs. Accordingly, we have investigated using computation and experiment the protein-monomer binding interactions that may influence the desired specificity. Myoglobin was used as the target protein and five different acrylamide-based monomers considered. Protein binding sites were predicted using SiteMap and binding free energies of monomers at each site calculated using MM-GBSA. Statistical thermodynamic analysis and study of atomistic interactions facilitated rationalization of monomer performance in MIP rebinding studies (% rebind; imprinting factors). CD spectroscopy was used to determine monomer effects on myoglobin secondary structure, with all monomers except the smallest monomer (acrylamide) causing significant changes. A complex interplay between different protein-monomer binding effects and MIP efficacy was observed. Validation of hypotheses for key binding features was achieved by rational selection of two different co-monomer MIP combinations that produced experimental results in agreement with predictions. The co-monomer studies revealed that uniform, non-competitive binding of monomers around a target protein is favourable. This study represents a step towards future rational in silico design of MIPs for proteins

Structure based inhibitor design targeting glycogen phosphorylase b. Virtual screening, synthesis, biochemical and biological assessment of novel N-acyl-β-d-glucopyranosylamines

Glycogen phosphorylase (GP) is a validated target for the development of new type 2 diabetes treatments. Exploiting the Zinc docking database, we report the in silico screening of 1888 β- D-glucopyranose-NH-CO-R putative GP inhibitors differing only in their R groups. CombiGlide and GOLD docking programs with different scoring functions were employed with the best performing methods combined in a “consensus scoring” approach to ranking of ligand binding affinities for the active site. Six selected candidates from the screening were then synthesized and their inhibitory potency was assessed both in vitro and ex vivo. Their inhibition constants’ values, in vitro, ranged from 5 to 377 µM while two of them were effective at causing inactivation of GP in rat hepatocytes at low µM concentrations. The crystal structures of GP in complex with the inhibitors were defined and provided the structural basis for their inhibitory potency and data for further structure based design of more potent inhibitors

Στρατηγικός σχεδιασμός της Δημόσιας Διοίκησης και των εμπλεκομένων φορέων σε θέματα που άπτονται της Οργανωμένης Απομάκρυνσης Πληθυσμού, συνέπεια μιας φυσικής ή τεχνολογικής καταστροφής. Αξιολόγηση, συμπεράσματα και προτάσεις.

Παράλληλη με τη γέννηση και εξέλιξη της ανθρωπότητας είναι και η εμφάνιση καταστροφών και μάλιστα με αυξητικές τάσεις δεδομένης και της ύπαρξης πλήθους κινδύνων, τόσο φυσικών όσο και ανθρωπογενών. Η αρχικά έμφυτη ανάγκη του ανθρώπου να αμυνθεί στα καταστροφικά φαινόμενα έχει εξελιχθεί σήμερα σε υποχρέωση κάθε οργανωμένης Πολιτείας, η οποία εντάσσει στην άσκηση της πολιτικής της και τον τομέα της Διαχείρισης Κρίσεων και Καταστροφών. Στην Ελλάδα αυτός ο τομέας ανήκει στην Πολιτική Προστασία η οποία αναπτύσσει προς αντιμετώπιση των καταστροφών σειρά δράσεων, μία από τις οποίες είναι και η Οργανωμένη Απομάκρυνση Πληθυσμού (Ο.Α.Π.). Η Ο.Α.Π. θεσπίστηκε το 2007 και σκοπό της αποτελεί η προστασία της ζωής και της υγείας των πολιτών από την απειλή μιας εξελισσόμενης ή επικείμενης καταστροφής. Στα πλαίσια της παρούσας εργασίας μελετάται ο στρατηγικός σχεδιασμός εκ μέρους της Δημόσιας Διοίκησης και των εμπλεκόμενων φορέων. Καταγράφεται το θεσμικό πλαίσιο της Ο.Α.Π., παρουσιάζονται τα στάδια αυτής, αναλύονται τα χαρακτηριστικά της και αποτυπώνεται η εφαρμογή όλων αυτών στην πράξη με τη μελέτη περίπτωσης εφαρμογής της η οποία έλαβε χώρα το 2017 στην πόλη της Θεσσαλονίκης. Επιπλέον, γίνεται μια σύντομη παρουσίαση του τομέα της Ιδιωτικής Ασφάλειας στην Ελλάδα και προτείνεται ο τρόπος με τον οποίο το προσωπικό αυτού θα μπορούσε να χρησιμοποιηθεί κατά την εφαρμογή μιας τέτοιας δράσης αλλά και ευρύτερα στα πλαίσια της Πολιτικής Προστασίας. Τέλος, γίνεται μια αξιολόγηση όλων των δεδομένων που παρουσιάζονται στην παρούσα εργασία, εξάγονται συμπεράσματα και παρατίθενται προτάσεις προς βελτίωση του στρατηγικού σχεδιασμού της Ο.Α.Π.Parallel to the birth and evolution of mankind is the emergence of disasters, and even with increasing tendencies given the existence of many hazards, both natural and man-made. The originally inherent human need to defend itself in the devastating phenomena has now evolved into an obligation of any organized State which is involved in the conduct of its policy and the field of Crisis and Disaster Management. In Greece, this sector belongs to Civil Protection, which develops a series of actions to combat disasters, one of which is Organized Population Evacuation (O.P.E.). The O.P.E. was introduced in 2007 and aims to protect the lives and health of citizens from the threat of an evolving or imminent disaster. In this paper, strategic planning by stakeholders is being studied. The institutional framework of the O.P.E. is recorded, its stages are presented, its characteristics are analyzed and the implementation of all these in practice is illustrated by the case study of its implementation which took place in 2017 in the city of Thessaloniki. In addition, there is a brief presentation of the Private Security Sector in Greece and it is suggested that its staff could be used in the implementation of such an action but also in the wider context of Civil Protection. Finally, an evaluation of all the data presented in the present work is made, conclusions are drawn and proposals are presented to improve the strategic planning of the O.P.E