The Unfolding MD Simulations of Cyclophilin: Analyzed by Surface Contact Networks and Their Associated Metrics

Currently, considerable interest exists with regard to the dissociation of close packed aminoacids within proteins, in the course of unfolding, which could result in either wet or dry moltenglobules. The progressive disjuncture of residues constituting the hydrophobic core ofcyclophilin from L. dono...

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Bibliographic Details
Published in:PloS one 2015-11, Vol.10 (11), p.e0142173-e0142173
Main Authors: Roy, Sourav, Basu, Sankar, Dasgupta, Dipak, Bhattacharyya, Dhananjay, Banerjee, Rahul
Format: Article
Language:English
Subjects:
Amino acids
Analysis
Complementarity
Cyclophilins - chemistry
Dihydrofolate reductase
Disintegration
Dissociation
Equilibrium
Flexibility
Hydrophobic and Hydrophilic Interactions
Hydrophobicity
Leishmania donovani
Leishmania donovani - chemistry
Molecular dynamics
Molecular Dynamics Simulation
Nuclear physics
Protein Conformation
Protein folding
Protein structure
Protein Structure, Secondary
Protein Unfolding
Proteins
Protozoan Proteins - chemistry
Residues
Surface Properties
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Summary:Currently, considerable interest exists with regard to the dissociation of close packed aminoacids within proteins, in the course of unfolding, which could result in either wet or dry moltenglobules. The progressive disjuncture of residues constituting the hydrophobic core ofcyclophilin from L. donovani (LdCyp) has been studied during the thermal unfolding of the molecule, by molecular dynamics simulations. LdCyp has been represented as a surface contactnetwork (SCN) based on the surface complementarity (Sm) of interacting residues within themolecular interior. The application of Sm to side chain packing within proteins make it a very sensitive indicator of subtle perturbations in packing, in the thermal unfolding of the protein. Network based metrics have been defined to track the sequential changes in the disintegration ofthe SCN spanning the hydrophobic core of LdCyp and these metrics prove to be highly sensitive compared to traditional metrics in indicating the increased conformational (and dynamical) flexibility in the network. These metrics have been applied to suggest criteria distinguishing DMG, WMG and transition state ensembles and to identify key residues involved in crucial conformational/topological events during the unfolding process.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0142173