Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	Assessing sequence reversal effects on coiled-coil stability using AI-based structure prediction and enhanced sampling atomistic simulations
Δημιουργός/Συγγραφέας:	Arnittali, Maria Markopoulou, Elena Harmandaris, Vagelis [EL] Ρισάνου, Αναστασία[EN] Rissanou, Anastassia
Εκδότης:	The Royal Society of Chemistry
Ημερομηνία:	2026-10-02
Γλώσσα:	Αγγλικά
DOI:	10.1039/d6cp01691j
Άλλο:	42825582
Περίληψη:	This study investigates the impact of sequence inversion on the structural integrity and thermodynamic stability of the wtRop protein, a prototypical coiled-coil motif. We utilized AI-driven structure prediction (ColabFold) to generate initial models for the unknown rRop sequence, which yielded both parallel and antiparallel monomeric orientations. These models were subjected to classical molecular dynamics simulations and well-tempered metadynamics. The combination of atomistic simulations and enhanced sampling techniques allowed for the calculation of the free energy surface across four collective variables: (i) angle between the monomers, (ii) distance between the monomer's center of mass, (iii) helicity and (iv) torsion angle similarity, characterizing the energetic barriers and conformational transitions of the parallel rRop, the antiparallel rRop, and the parent wtRop systems. Free energy analysis reveals that both rRop models deviate from the native antiparallel orientation to stabilize at an intermediate angle. Notably, the antiparallel variant exhibits the most significant instability, characterized by increased monomer separation and a more pronounced loss of secondary structure relative to the wild-type and the parallel model. While both reversed sequences show a reduction in α-helicity compared to wtRop, the antiparallel model demonstrates a more pronounced loss of structural integrity, characterized by a disrupted hydrogen bond network, increased solvent-accessible surface area, and the failure to maintain a robust hydrophobic core. Free energy calculations further confirmed that the parallel variant shares greater conformational similarity with the parent protein.
Τίτλος πηγής δημοσίευσης:	Physical chemistry chemical physics : PCCP
Θεματική Κατηγορία:	[EL] Βιοπληροφορική[EN] Bioinformatics [EL] Δομική Βιολογία[EN] Structural Biology
Λέξεις-Κλειδιά:	computational biology artificial intelligence protein structure prediction protein biophysics atomistic molecular dynamics
Κάτοχος πνευματικών δικαιωμάτων:	© 2026 The Author(s). Published by the Royal Society of Chemistry on behalf of the Owner Societies
Όροι και προϋποθέσεις δικαιωμάτων:	This article is licensed under a Creative Commons Attribution 4.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.
Ηλεκτρονική διεύθυνση στον εκδότη (link):	https://doi.org/10.1039/d6cp01691j
Εμφανίζεται στις συλλογές:	Ινστιτούτο Θεωρητικής και Φυσικής Χημείας (ΙΘΦΧ) - Επιστημονικό έργο