Fast, Accurate, and System-Specific Variable-Resolution Modeling of Proteins

R. Fiorentini, T. Tarenzi, R. Potestio, Fast, Accurate, and System-Specific Variable-Resolution Modeling of Proteins, J. Chem. Inf. Model. (2023)

In recent years, a few multiple-resolution modeling strategies have been proposed, in which functionally relevant parts of a biomolecule are described with atomistic resolution, with the remainder of the system being concurrently treated using a coarse-grained model. In most cases, the parametrization of the latter requires lengthy reference all-atom simulations and/or the usage of off-shelf coarse-grained force fields, whose interactions have to be refined to fit the specific system under examination. Here, we overcome these limitations through a novel multiresolution modeling scheme for proteins, dubbed coarse-grained anisotropic network model for variable resolution simulations, or CANVAS. This scheme enables a user-defined modulation of the resolution level throughout the system structure; a fast parametrization of the potential without the necessity of reference simulations; and the straightforward usage of the model on the most commonly used molecular dynamics platforms. The method is presented and validated with two case studies, the enzyme adenylate kinase and the therapeutic antibody pembrolizumab, by comparing the results obtained with the CANVAS model against fully atomistic simulations. The modeling software, implemented in Python, is made freely available for the community on a collaborative github repository.