Biomaterial Database

Microsecond molecular dynamics simulation of guanidinium chloride induced unfolding of ubiquitin. 2014

Manoj Mandal, and Chaitali Mukhopadhyay

Department of Chemistry, University of Calcutta, 92, A.P.C. Road, Kolkata - 700 009, India. chaitalicu@yahoo.com cmchem@caluniv.ac.in.

An all atom molecular dynamics simulation was used to explore the atomic detail mechanism of guanidinium induced unfolding of the protein ubiquitin. Ubiquitin unfolds through pre-unfolded (intermediate) states, i.e. guanidinium induced unfolding of ubiquitin appears to be a multi-step process, and loss of hydrophobic contacts of C-terminal residues is crucial for ubiquitin unfolding. Free-energy landscapes show that barrier separation between folded and unfolded basins is ∼5.0 kcal mol(-1), and both the basins are of comparable energy. It was observed that guanidinium ions interact directly with ubiquitin. Favorable electrostatic interaction is the main driving force for such accumulation of guanidinium ions near protein, but van der Waals energy also contributes. RDF plots show that accumulation of guanidinium ions near specific residues is the main cause for destabilization of intra-residue interactions crucial to maintain the three-dimensional fold of the protein. One salt-bridge interaction between Lys11 and Glu34 appears to be important to maintain the crystal structure of ubiquitin and this salt-bridge can map the unfolding process of ubiquitin.

UI	MeSH Term	Description	Entries
D008958	Models, Molecular	Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.	Molecular Models,Model, Molecular,Molecular Model
D012997	Solvents	Liquids that dissolve other substances (solutes), generally solids, without any change in chemical composition, as, water containing sugar. (Grant & Hackh's Chemical Dictionary, 5th ed)	Solvent
D013997	Time Factors	Elements of limited time intervals, contributing to particular results or situations.	Time Series,Factor, Time,Time Factor
D055672	Static Electricity	The accumulation of an electric charge on a object	Electrostatic,Electrostatics,Static Charge,Charge, Static,Charges, Static,Electricity, Static,Static Charges
D056004	Molecular Dynamics Simulation	A computer simulation developed to study the motion of molecules over a period of time.	Molecular Dynamics Simulations,Molecular Dynamics,Dynamic, Molecular,Dynamics Simulation, Molecular,Dynamics Simulations, Molecular,Dynamics, Molecular,Molecular Dynamic,Simulation, Molecular Dynamics,Simulations, Molecular Dynamics
D058767	Protein Unfolding	Conformational transitions of the shape of a protein to various unfolded states.	Unfolding, Protein
D019791	Guanidine	A strong organic base existing primarily as guanidium ions at physiological pH. It is found in the urine as a normal product of protein metabolism. It is also used in laboratory research as a protein denaturant. (From Martindale, the Extra Pharmacopoeia, 30th ed and Merck Index, 12th ed) It is also used in the treatment of myasthenia and as a fluorescent probe in HPLC.	Guanidine Hydrochloride,Guanidinium,Guanidinium Chloride,Guanidine Monohydrate,Guanidine Monohydrobromide,Guanidine Monohydrochloride,Guanidine Monohydroiodine,Guanidine Nitrate,Guanidine Phosphate,Guanidine Sulfate,Guanidine Sulfate (1:1),Guanidine Sulfate (2:1),Guanidine Sulfite (1:1),Guanidium Chloride,Chloride, Guanidinium,Chloride, Guanidium,Hydrochloride, Guanidine,Monohydrate, Guanidine,Monohydrobromide, Guanidine,Monohydrochloride, Guanidine,Monohydroiodine, Guanidine,Nitrate, Guanidine,Phosphate, Guanidine,Sulfate, Guanidine
D025801	Ubiquitin	A highly conserved 76-amino acid peptide universally found in eukaryotic cells that functions as a marker for intracellular PROTEIN TRANSPORT and degradation. Ubiquitin becomes activated through a series of complicated steps and forms an isopeptide bond to lysine residues of specific proteins within the cell. These "ubiquitinated" proteins can be recognized and degraded by proteosomes or be transported to specific compartments within the cell.	APF-1,ATP-Dependent Proteolysis Factor 1,HMG-20,High Mobility Protein 20,Ubiquitin, Human,ATP Dependent Proteolysis Factor 1,Human Ubiquitin