title: MM/PBSA analysis of molecular dynamics simulations of bovine beta-lactoglobulin: free energy gradients in conformational transitions?
abstract: The pH-driven opening and closure of beta-lactoglobulin EF loop, acting as a lid and closing the internal cavity of the protein, has been studied by molecular dynamics (MD) simulations and free energy calculations based on molecular mechanics/Poisson-Boltzmann (PB) solvent-accessible surface area (MM/PBSA) methodology. The forms above and below the transition pH differ presumably only in the protonation state of residue Glu89. MM/PBSA calculations are able to reproduce qualitatively the thermodynamics of the transition. The analysis of MD simulations using a combination of MM/PBSA methodology and the colony energy approach is able to highlight the driving forces implied in the transition. The analysis suggests that global rearrangements take place before the equilibrium local conformation is reached. This conclusion may bear general relevance to conformational transitions in all lipocalins and proteins in general.
authors.affiliation: Dipartimento Scientifico e Tecnologico, Università di Verona, Verona, Italy. fogolari@dstb.uniud.it <fogolari@dstb.uniud.it>
authors.forename: Federico
authors.initials: F
authors.lastname: Fogolari
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Moroni
authors.forename: Marcin
authors.initials: M
authors.lastname: Wojciechowski
authors.forename: Maciej
authors.initials: M
authors.lastname: Baginski
authors.forename: Laura
authors.initials: L
authors.lastname: Ragona
authors.forename: Henriette
authors.initials: H
authors.lastname: Molinari
mesh_terms: D000818:Animals; D002417:Cattle; D003198:Computer Simulation; D007782:Lactoglobulins / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D017510:Protein Folding; D013314:Stress, Mechanical; D013816:Thermodynamics
chemical_list: D007782:Lactoglobulins