DNA repair-related diseases, such as xeroderma pigmentosum (XP), trichothiodystrophy (TTD), Cockayne syndrome (CS), Cerebro-oculo-facio-skeletal syndrome (COFS), which are associated with impairments in the nucleotide excision repair (NER) pathway [1], [2], [3], [4], [5], are all related to specific mutations that affect the proteins associated to NER, influencing protein-protein interactions (PPI), catalysis, and/or DNA-binding. Hence, understanding the molecular behavior of NER-related proteins becomes essential to uncover how these diseases cause their phenotypes and how NER is organized.

However, describing a protein's structural information goes beyond identifying domains and residues that play indispensable roles in their functions. Proteins are dynamic macromolecules that undergo conformational changes in response to different stimuli and binding partners. Although multiple methods exist to elucidate a protein 3D structure, observing their dynamic molecular behavior in a continuous timescale outside bioinformatics is still unattainable. Molecular dynamics (MD) simulations have been broadly employed to witness the molecular behavior of proteins and the study of proteins bound to different DNA conformations, mainly those containing mutated sequences, shedding light on lesion recognition. For these and other reasons, MD analyses have become an indispensable part of the ``structural biologist'' toolkit. However, as popular as they are, MD studies focusing on DNA repair have yet to be more widespread.

While some works provide explanations of their strengths [6], [7] and/or limitations [8], there are no reviews articles compiling the advancements made in molecular dynamics approaches applied to NER and discussing: (i) how this technique is currently employed in the field of DNA repair, focusing on NER proteins; (ii) which technical setups are being employed, their strengths and limitations; (iii) which insights or information are they providing to understand the NER pathway or NER-associated proteins; (iv) which open questions would be suited for this technique to answer; and (v) where can we go from here. In this work, we will tackle these questions, revising and critically discussing the results published in the context of NER proteins. We will focus on the core canonical proteins described as essential protagonists: the XPA to XPG proteins and their major molecular partners (RAD23B, CETN2, DDB1, TFIIH, ERCC1, RPA70, RPA32, and RPA14). MD works performed exclusively in DNA models were not considered. We hope that the debate conducted in this work aid in the decision-making process of new research applying macromolecule simulation in DNA repair-associated diseases.