Combining the MARTINI and Structure-Based Coarse-Grained Approaches for the Molecular Dynamics Studies of Conformational Transitions in Proteins

• Published in: Journal of chemical theory and computation Vol. 13; no. 3; pp. 1366 - 1374
• Main Authors: Poma, Adolfo B, Cieplak, Marek, Theodorakis, Panagiotis E
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 14.03.2017
• Subjects: Bonding; Computer simulation; Contact; Cut-off; Harmonics; Mathematical models; Molecular Dynamics Simulation; Organometallic Compounds - chemistry; Protein Conformation; Proteins; Proteins - chemistry; Quantum Theory; Spring constant
• ISSN: 1549-9618; 1549-9626
• DOI: 10.1021/acs.jctc.6b00986

The application of coarse-grained (CG) models in biology is essential to access large length and time scales required for the description of many biological processes. The ELNEDIN protein model is based on the well-known MARTINI CG force-field and incorporates additionally harmonic bonds of a certain spring constant within a defined cutoff distance between pairs of residues, in order to preserve the native structure of the protein. In this case, the use of unbreakable harmonic bonds hinders the study of unfolding and folding processes. To overcome this barrier we have replaced the harmonic bonds with Lennard–Jones interactions based on the contact map of the native protein structure as is done in Go̅-like models. This model exhibits very good agreement with all-atom simulations and the ELNEDIN. Moreover, it can capture the structural motion linked to particular catalytic activity in the Man5B protein, in agreement with all-atom simulations. In addition, our model is based on the van der Waals radii, instead of a cutoff distance, which results in a smaller contact map. In conclusion, we anticipate that our model will provide further possibilities for studying biological systems based on the MARTINI CG force-field by using advanced-sampling methods, such as parallel tempering and metadynamics.