Coarse-Grained Simulations of Heme Proteins: Validation and Study of Large Conformational Transitions

Abstract

Heme proteins are ubiquitous in nature and perform many diverse functions in all kingdoms of life. Many of these functions are related to large-scale conformational transitions and allosteric processes. Sampling of these large conformational changes is computationally very challenging. In this context, coarse-grain simulations emerge as an efficient approach to explore the conformational landscape. In this work, we present a coarse-grained model of the heme group and thoroughly validate this model in different benchmark examples, which include the monomeric heme proteins myoglobin and neuroglobin and the tetrameric human hemoglobin where we evaluated the method's ability to explore conformational changes (as the formation of hexacoordinated species) and allosteric transitions (as the well-known R → T transition). The obtained results are compared with atomistic molecular dynamics simulations. Overall, the results indicate that this approach conserves the essential dynamical information on different allosteric processes.

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Multiscale approach to the activation and phosphotransfer mechanism of CpxA histidine kinase reveals a tight coupling between conformational and chemical steps

“…Initial structures were converted to the CG representation, minimized, and slowly thermalized to the desired temperature using the Langevin thermostat. Coarse grain ATP parametrization was performed as described in our previous work [27] and parameters are available under request. All simulations were performed at constant pressure using Berendsen barostat.…”

Molecular and Coarse-Grained Modeling to Characterize and Optimize Dendrimer-Based Nanocarriers for Short Interfering RNA Delivery

“…Validation analysis was performed taking into account the last 20 ns of production run, following two main strategies: (A) suit the bonded parameters as similar as possible to the atomistic models and (B) try to optimize the conformational features of the dendrimers as close as possible to the atomistic simulations. 70,78,79 The detailed validation procedure that has been adopted can be found in the Supporting Information S.4.…”