REGULAR ARTICLE MD simulations of plant hemoglobins: the hexa- to penta-coordinate structural transition Mariano Andrea Scorciapino • Claire Wallon • Matteo Ceccarelli Received: 7 June 2011 / Accepted: 12 September 2011 / Published online: 4 October 2011 Ó Springer-Verlag 2011 Abstract Hemoglobins are ubiquitous proteins found in bacteria, plants, and animals with diverse functions other than the classical transport/storage of oxygen. Different functions are expected to correspond to substantially dif- ferent structures, such as the hexa- and penta-coordination of the iron atom. It is now widely believed that pentaco- ordinate hemoglobins evolved from the hexacoordinate ones, both in plants and in animals. Since plant hemoglo- bins evolved more recently than in animals, they represent a simpler and thus useful system to investigate protein sequence/structure features that specifically supported, guided by molecular evolution, the capacity for oxygen transport. In the present work, we selected a fully hexa- coordinate globin, AHb2 from Arabidopsis thaliana and the pentacoordinate oxygen-transporting LegHb from yellow lupin, that share a high degree of sequence identity. Our aim is to identify the structural determinants for oxygen transport by analyzing the structural/dynamical differences of a hexacoordinate and a pentacoordinate globin using all- atom molecular dynamics simulations. Using comparative MD simulations, we were able to go beyond the simple sequence alignment, pointing out important differences between these two hemoglobins especially at the level of the CD region, whose dynamics was found, in turn, to be strongly correlated with that of the distal region. Keywords Molecular dynamics Á Oxygen transport Á Plant hemoglobins 1 Introduction The globins family represents a nice example of proteins that, through evolution, diversified their functions. Hemoglobin (Hb), probably the most important protein of this family, is an oxygen binding protein that is present in most living organisms. Hbs were originally described in animals, and in particular, in vertebrates they have been shown to facilitate oxygen transport in blood. However, animals, plants, fungi, and bacteria express a number of different Hbs [1], many of which have functions other than the oxygen transport [2, 3]. These different functions correspond to substantially differ- ent structures, some of these globins being monomeric, some others being characterized by a multimeric quaternary structure. Recent genomic studies [4] proposed Hbs to have originated in a bacterial ancestor, which probably needed to sequester reduced iron on one side and to control excessive oxygen concentrations, lethal for the anaerobic life, on the other. Another possible function may have been the detoxi- fication of nitric oxide through its oxidation in an oxygen- rich successive environment. From bacteria, possibly through lateral gene transfer or some other mechanism, this Hb ancestor appeared in animals (*500 Myears) and more recently in plants (*200 Myears) [1, 5, 6]. It has been rec- ognized that natural selection and evolution through Dedicated to Professor Akira Imamura on the occasion of his 77th birthday and published as part of the Imamura Festschrift Issue. Electronic supplementary material The online version of this article (doi:10.1007/s00214-011-1041-6) contains supplementary material, which is available to authorized users. M. A. Scorciapino Dipartimento di Scienze Chimiche, University of Cagliari, Monserrato, Italy M. A. Scorciapino Á M. Ceccarelli Istituto Officina del Materiali, SLACS, CNR, Monserrato, Italy C. Wallon Á M. Ceccarelli (&) Dipartimento di Fisica, University of Cagliari, Monserrato, Italy e-mail: matteo.ceccarelli@dsf.unica.it 123 Theor Chem Acc (2011) 130:1105–1114 DOI 10.1007/s00214-011-1041-6