Журнал компьютерных наук и системной биологии

Molecular Modeling of Heat Shock Protein of 60-Kda from Paracoccidioides Brasiliensis: The First in silico Structural Model of a Fungal Hsp60

Abstract

Fabrício Freitas Fernandes, Renata Ariza Marques Rossetti, Arlete Coelho-Castelo and Ademilson Panunto-Castelo

Paracoccidioides brasiliensis is a dimorphic fungus that causes paracoccidioido mycosis (PCM), an endemic mycosis in Latin America. PCM is a chronic, granulomatous, and progressive disease, which has a wide clinical spectrum of manifestations. Although it knows that the main clinical forms are consequences of fungus-host interaction, immune response in PCM is still an open field. The antigenic complexity of P. brasiliensis and the role of most antigens have been poorly explored, thereby decreasing the chances of finding vaccine and therapeutic targets for PCM. Recent results from our group have shown that heat shock protein of 60-kDa from P. brasiliensis strain 18 (Hsp60_Pb18) has a possible detrimental effect on the course of the PCM. Here, we show the molecular model of Hsp60_Pb18 that was generated with the program MODELLER9V8. The model validation was performed using PROCHECK and VERIFY3D. According to the results, the three-dimensional structure of Hsp60_Pb18 is a high reliability model, which displays a remarkable similarity with the three distinct domains of GroEL subunit-equatorial, intermediate and apical domains. This study will provide direction and continuity of studies to characterize Hsp60_ Pb18 and their domains, and thus contribute to the knowledge of the fungus biology and to determine vaccines and/ or therapeutic targets.