Coarse-Grained Simulations of Heme Proteins: Validation and Study of Large Conformational Transitions.
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.
Dto. de Química Inorgánica, Analítica y Química Física, Fac. de Ciencias Exactas y Naturales, Univ. de Buenos Aires/INQUIMAE-CONICET , Buenos Aires, C1428EGA, Argentina.|Dto. de Química Biologica Fac. de Ciencias Exactas y Naturales, Univ. de Buenos Aires/IQUIBICEN-CONICET , Buenos Aires, C1428EGA, Argentina.
Claudia L
CL
Ramírez
Dto. de Química Inorgánica, Analítica y Química Física, Fac. de Ciencias Exactas y Naturales, Univ. de Buenos Aires/INQUIMAE-CONICET , Buenos Aires, C1428EGA, Argentina.
Ariel
A
Petruk
Dto. de Química Inorgánica, Analítica y Química Física, Fac. de Ciencias Exactas y Naturales, Univ. de Buenos Aires/INQUIMAE-CONICET , Buenos Aires, C1428EGA, Argentina.
Mauro
M
Bringas
Dto. de Química Inorgánica, Analítica y Química Física, Fac. de Ciencias Exactas y Naturales, Univ. de Buenos Aires/INQUIMAE-CONICET , Buenos Aires, C1428EGA, Argentina.
Dario A
DA
Estrin
Department of Chemistry, University of Florida , Gainesville, Florida 32611-7200, United States.
Adrian E
AE
Roitberg
Dto. de Química Biologica Fac. de Ciencias Exactas y Naturales, Univ. de Buenos Aires/IQUIBICEN-CONICET , Buenos Aires, C1428EGA, Argentina.
Marcelo A
MA
Marti
Dto. de Química Inorgánica, Analítica y Química Física, Fac. de Ciencias Exactas y Naturales, Univ. de Buenos Aires/INQUIMAE-CONICET , Buenos Aires, C1428EGA, Argentina.
Luciana
L
Capece
D006418:Heme / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D015203:Reproducibility of Results
D011506:Proteins; D006418:Heme