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Abstract:
We present a review of a series of contact maps for the determination of native interactions in proteins and nucleic acids based on a distance threshold. Such contact maps are mostly based on physical and chemical construction, and yet they are sensitive to some parameters (e.g., distances or atomic radii) and can neglect some key interactions. Furthermore, we also comment on a new class of contact maps that only requires geometric arguments. The contact map is a necessary ingredient to build a robust Gō-Martini model for proteins and their complexes in the Martini 3 force field. We present the extension of a popular structure-based Gō--like approach to the study of protein–sugar complexes, and the limitations of this approach are also discussed. The Gō-Martini approach was first introduced by Poma et al. (J. Chem. Theory Comput. 13, 1366 (2017)) in Martini 2 force field, and recently, it has gained the status of gold standard for protein simulation undergoing conformational changes in Martini 3 force field. We discuss several studies that have provided support for this approach in the context of the biophysical community.

Keywords:
Martini 3,Structure-based coarse-graining,SMFS,biomolecules,GoMartini

Abstract:
The SARS-CoV-2 pandemic spurred numerous research endeavors to comprehend the virus and mitigate its global severity. Understanding the binding interface between the virus and human receptors is pivotal to these efforts and paramount to curbing infection and transmission. Here we employ atomic force microscopy and steered molecular dynamics simulation to explore SARS-CoV-2 receptor binding domain (RBD) variants and angiotensin-converting enzyme 2 (ACE2), examining the impact of mutations at key residues upon binding affinity. Our results show that the Omicron and Delta variants possess strengthened binding affinity in comparison to the Mu variant. Further, using sera from individuals either vaccinated or with acquired immunity following Delta strain infection, we assess the impact of immunity upon variant RBD/ACE2 complex formation. Single-molecule force spectroscopy analysis suggests that vaccination before infection may provide stronger protection across variants. These results underscore the need to monitor antigenic changes in order to continue developing innovative and effective SARS-CoV-2 abrogation strategies.

Keywords:
SARS-Cov-2,Molecular Dynamics ,Immunity,SMFS,Nanomechanics,Free Energy,Jarzynski,Receptor,Protein complex,interfaces