Extrapolation of Inter Domain Communications and Substrate Binding Cavity of Camel HSP70 1A: A Molecular Modeling and Dynamics Simulation Study

• Published in: PloS one Vol. 10; no. 8; p. e0136630
• Main Authors: Gupta, Saurabh, Rao, Atmakuri Ramakrishna, Varadwaj, Pritish Kumar, De, Sachinandan, Mohapatra, Trilochan
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 27.08.2015; Public Library of Science (PLoS)
• Subjects: Animals; Binding; Bioinformatics; Camelus; Capra hircus; Caprinae; Cold-Shock Response - physiology; Communication; Computer Simulation; DnaK protein; Docking; E coli; Escherichia coli; Gene expression; Genomics; Heat shock proteins; Heat-Shock Response - physiology; Hsp110 protein; HSP70 Heat-Shock Proteins - chemistry; HSP70 Heat-Shock Proteins - genetics; HSP70 Heat-Shock Proteins - metabolism; Hsp70 protein; Information technology; Modelling; Molecular chains; Molecular Docking Simulation; Molecular dynamics; Molecular Dynamics Simulation; Molecular modelling; Monopterus albus; Peptides; Principal components analysis; Protein folding; Protein structure; Protein Structure, Tertiary; Protein transport; Saccharomyces cerevisiae; Simulation; Stress; Stresses; Structure-function relationships; Substrates; Three dimensional models; Translocation; India
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0136630

Heat shock protein 70 (HSP70) is an important chaperone, involved in protein folding, refolding, translocation and complex remodeling reactions under normal as well as stress conditions. However, expression of HSPA1A gene in heat and cold stress conditions associates with other chaperons and perform its function. Experimental structure for Camel HSP70 protein (cHSP70) has not been reported so far. Hence, we constructed 3D models of cHSP70 through multi- template comparative modeling with HSP110 protein of S. cerevisiae (open state) and with HSP70 protein of E. coli 70kDa DnaK (close state) and relaxed them for 100 nanoseconds (ns) using all-atom Molecular Dynamics (MD) Simulation. Two stable conformations of cHSP70 with Substrate Binding Domain (SBD) in open and close states were obtained. The collective mode analysis of different transitions of open state to close state and vice versa was examined via Principal Component Analysis (PCA) and Minimum Distance Matrix (MDM). The results provide mechanistic representation of the communication between Nucleotide Binding Domain (NBD) and SBD to identify the role of sub domains in conformational change mechanism, which leads the chaperone cycle of cHSP70. Further, residues present in the chaperon functioning site were also identified through protein-peptide docking. This study provides an overall insight into the inter domain communication mechanism and identification of the chaperon binding cavity, which explains the underlying mechanism involved during heat and cold stress conditions in camel.