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

C.L. RAMIREZ; A. PETRUK; M. BRINGAS; D.A. ESTRIN; A.E. ROITBERG; M.A. MARTI; L. CAPECE

JOURNAL OF CHEMICAL THEORY AND COMPUTATION

AMER CHEMICAL SOC

Lugar: Washington; Año: 2016 vol. 12 p. 3390 - 3397

1549-9618

Heme proteins are ubiquitous in nature and perform many diverse functions in all kingdoms of life. Many of thesefunctions are related to large-scale conformational transitions and allosteric processes. Sampling of these large conformationalchanges is computationally very challenging. In this context, coarse-grain simulations emerge as an efficient approach to explorethe conformational landscape. In this work, we present a coarse-grained model of the heme group and thoroughly validate thismodel in different benchmark examples, which include the monomeric heme proteins myoglobin and neuroglobin and thetetrameric human hemoglobin where we evaluated the method?s ability to explore conformational changes (as the formation ofhexacoordinated species) and allosteric transitions (as the well-known R → T transition). The obtained results are comparedwith atomistic molecular dynamics simulations. Overall, the results indicate that this approach conserves the essential dynamicalinformation on different allosteric processes.