title: Computational tools for analysing structural changes in proteins in solution.
abstract: Many important structural changes in proteins involve long-time dynamics, which are outside the timescale presently accessible by a straightforward integration of Newton's equations of motion. This problem is addressed with minimisation-based algorithms, which are applied on possible reaction pathways using atomic-detail models. For reasons of efficiency, an implicit treatment of solvent is imperative. We present the charge reparameterisation protocol, which is a method that approximates the interaction energies obtained by a numerical solution of the Poisson-Boltzmann equation. Furthermore, we present a number of methods that can be used to compute possible reaction pathways associated with a particular conformational change. Two of them, the self-penalty walk and the nudged elastic band method, define an objective function, which is minimised to find optimal paths. A third method, conjugate peak refinement, is a heuristic method, which finds minimum energy paths without the use of an explicit objective function. Finally, we discuss problems and limitations with these methods and give a perspective on future research.
authors.affiliation: Interdisciplinary Research Center for Scientific Computing (IWR), Computational Molecular Biophysics Group, University of Heidelberg, Heidelberg, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Noé
authors.forename: Sonja M
authors.initials: SM
authors.lastname: Schwarzl
authors.forename: Stefan
authors.initials: S
authors.lastname: Fischer
authors.forename: Jeremy C
authors.initials: JC
authors.lastname: Smith
mesh_terms: D000465:Algorithms; D003198:Computer Simulation; D030562:Databases, Protein; D004735:Energy Transfer; D008958:Models, Molecular; D009038:Motion; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry* / Q000145:classification / Q000235:genetics; D040901:Proteomics / Q000379:methods*; D016415:Sequence Alignment / Q000379:methods; D020539:Sequence Analysis, Protein / Q000379:methods*; D012996:Solutions; D012997:Solvents / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D011506:Proteins; D012996:Solutions; D012997:Solvents