| Partner: Siewert J. Marrink |
Ostatnie publikacje
| 1. | Souza P.♦, Borges-Araújo L.♦, Christopher B.♦, Rodrigo A M.♦, Fabian G.♦, Peter P.♦, Liguo W.♦, Hafez R.♦, Borges-Araújo A.♦, Cofas Vargas L., Luca M.♦, Raúl M.♦, Melo M.♦, Sangwook W.♦, Marrink S.♦, Poma A., Sebastian T.♦, GōMartini 3: From large conformational changes in proteins to environmental bias corrections, Nature Communications, ISSN: 2041-1723, DOI: 10.1038/s41467-025-58719-0, Vol.16, No.4051, pp.1-19, 2025 Streszczenie: Coarse-grained modeling has become an important tool to supplement experimental measurements, allowing access to spatio-temporal scales beyond all-atom based approaches. The GōMartini model combines structure- and physics-based coarse-grained approaches, balancing computational efficiency and accurate representation of protein dynamics with the capabilities of studying proteins in different biological environments. This paper introduces an enhanced GōMartini model, which combines a virtual-site implementation of Gō models with Martini 3. The implementation has been extensively tested by the community since the release of the reparametrized version of Martini. This work demonstrates the capabilities of the model in diverse case studies, ranging from protein-membrane binding to protein-ligand interactions and AFM force profile calculations. The model is also versatile, as it can address recent inaccuracies reported in the Martini protein model. Lastly, the paper discusses the advantages, limitations, and future perspectives of the Martini 3 protein model and its combination with Gō models. Słowa kluczowe: GōMartini 3, Martini 3, Coarse graining, Proteins, IDP, membranes, Molecular Dynamics, Nanomechanics Afiliacje autorów:
|  | 200p. | |||||||||||||||||||||||||||||||||||||||||||||||||||
| 2. | Cofas Vargas L. F., Olivos-Ramirez G. E., Chwastyk M.♦, Moreira R.A.♦, Baker J. L.♦, Marrink S. J.♦, Poma Bernaola A.M., Nanomechanical footprint of SARS-CoV-2 variants in complex with a potent nanobody by molecular simulations, NANOSCALE, ISSN: 2040-3364, DOI: 10.1039/D4NR02074J, Vol.16, No.40, pp.18824-18834, 2024 Streszczenie: Rational design of novel antibody therapeutics against viral infections such as coronavirus relies on surface complementarity and high affinity for their effectiveness. Here, we explore an additional property of protein complexes, the intrinsic mechanical stability, in SARS-CoV-2 variants when complexed with a potent antibody. In this study, we utilized a recent implementation of the GōMartini 3 approach to investigate large conformational changes in protein complexes with a focus on the mechanostability of the receptor-binding domain (RBD) from WT, Alpha, Delta, and XBB.1.5 variants in complex with the H11-H4 nanobody. The analysis revealed moderate differences in mechanical stability among these variants. Also, we identified crucial residues in both the RBD and certain protein segments in the nanobody that contribute to this property. By performing pulling simulations and monitoring the presence of specific native and non-native contacts across the protein complex interface, we provided mechanistic insights into the dissociation process. Force-displacement profiles indicate a tensile force clamp mechanism associated with the type of protein complex. Our computational approach not only highlights the key mechanostable interactions that are necessary to maintain overall stability, but it also paves the way for the rational design of potent antibodies that are mechanostable and effective against emergent SARS-CoV-2 variants. Słowa kluczowe: SARS-CoV-2, GōMartini 3, Nanomechanics, Protein complexes, protein engineering, MD, native contacts Afiliacje autorów:
| | 140p. |