Configurational Entropy Reallocation and Complex Loop Dynamics of the Mosquito-Stage Pvs25 Protein Complexed with the Fab Fragment of the Malaria Transmission Blocking Antibody 2A8
Φόρτωση...
Ημερομηνία
Συγγραφείς
Σταυρακούδης, Αθανάσιος
Tsoulos, I. G.
Τίτλος Εφημερίδας
Περιοδικό ISSN
Τίτλος τόμου
Εκδότης
Περίληψη
Τύπος
Είδος δημοσίευσης σε συνέδριο
Είδος περιοδικού
peer reviewed
Είδος εκπαιδευτικού υλικού
Όνομα συνεδρίου
Όνομα περιοδικού
J Chem Theory Comput
Όνομα βιβλίου
Σειρά βιβλίου
Έκδοση βιβλίου
Συμπληρωματικός/δευτερεύων τίτλος
Περιγραφή
Pvs25 is a protein of unique 3D structure, and it is characterized by the presence of repeated EGF-like domains and 11 disulfide bonds. It is a very important candidate for the transmission-blocking malaria vaccine, as it plays an important role in mosquito infection by Plasmodium parasites. Recently, the X-ray structure of the protein complexed with the transmission blocking antibody 2A8 has been reported. In this study, we report the loop reorganization of the Pvs25 protein based on configurational entropy calculations and dihedral principal component analysis as revealed from the protein complex and free molecular dynamics simulations. While the total entropy of the protein was estimated to be almost the same in the free and complex trajectories, the partition of the entropy contribution in the loop fragments of the protein revealed interesting entropy reallocation after the 2A8 antibody binding. Interestingly, the 51-71 protein loop experienced a significant reduction in its configurational entropy, while other parts of the protein did not show any difference in it, or even showed an entropy increase. This trend in entropy redistribution was found to be in direct relationship with specific interactions with the antibody's binding site. Results from root-mean-square fluctuations/deviations and dihedral angle principal component analysis further support this finding.
Περιγραφή
Λέξεις-κλειδιά
molecular-dynamics, plasmodium-vivax, conformational entropy, vaccine candidates, energy landscape, ookinete surface, p-28 proteins, peptide, simulations, design
Θεματική κατηγορία
Παραπομπή
Σύνδεσμος
<Go to ISI>://000287049200024
http://pubs.acs.org/doi/abs/10.1021/ct100543c
http://pubs.acs.org/doi/abs/10.1021/ct100543c
Γλώσσα
en
Εκδίδον τμήμα/τομέας
Όνομα επιβλέποντος
Εξεταστική επιτροπή
Γενική Περιγραφή / Σχόλια
Ίδρυμα και Σχολή/Τμήμα του υποβάλλοντος
Πανεπιστήμιο Ιωαννίνων. Σχολή Οικονομικών και Κοινωνικών Επιστημών. Τμήμα Οικονομικών Επιστημών